cord-002070-8y24j34j	2016	Numerous investigators have reported the presence of MERS-CoV RNA or infectious virus in nasal swab specimens of dromedary camels in Saudi Arabia (3, 4, (8) (9) (10) , Qatar (5, (11) (12) (13) , Oman (14) , the United Arab Emirates (15), Nigeria (16) , and Egypt (17) . We have previously demonstrated that dromedary camels can be experimentally infected with MERS-CoV and found that mild upper respiratory tract disease associated with shedding copious amounts of virus by nasal secretions develops during the first week after infection (21) . We report characterization of an alpaca model of MERS-CoV infection in which we evaluated virus shedding and pathology, transmission by contact, and protective immunity 10 weeks after initial infection. Infectious virus was detected in nasal swab specimens from 2 of 3 alpacas co-housed with experimentally infected animals, and each of the 3 co-housed animals had neutralizing antibodies against MERS-CoV, which indicated virus transmission.
cord-007828-c7jxj74b	2014	Since the initial occurrence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, 1,2 the disease had caused 837 cases, with a case fatality rate of 34.7%. The World Health Organization (WHO) through its expert technical committees was prompt in developing its first infection control guidelines based on available knowledge on the new emerging virus, but it mostly drew on experience from a similar virus, severe acute respiratory syndrome coronavirus (SARS). Careful review of the recent increase in the number of cases revealed that about 25% were among HCWs. 4 Of the initial 128 recent MERS-CoV infected patients in Jeddah, Kingdom of Saudi Arabia, most (60%) were infected in the health care setting. Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients
cord-009476-4emc4o6n	2014	16 outbreak and prevent human-to-human and animalto-human transmission; an appropriate management algorithm, including best-practice guidelines for accurate diagnosis, infection control, intensive care, emergency medicine, and treatment; prioritise research related to the MERS-CoV outbreak such as case-control and cohort studies, seroprevalence studies, and clinical trials; and to eff ectively monitor outbreak control activities. 2 The new case defi nition (appendix) was developed based on reported health-care-associated MERS-CoV pneumonia (added as category 2 in the new case defi nition) and non-respiratory characteristics of patients with confi rmed infection who fi rst presented with acute febrile dengue-like illness with body aches, leucopenia, and thrombocytopenia (added as category 3). WHO Revised interim case defi nition for reporting to WHO-Middle East respiratory syndrome coronavirus (MERS-CoV): as of First confi rmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and Public Health Authorities
cord-009594-0rfbmi0q	2014	Late last year, the American Veterinary Medical Association held a forum called ''The Conversation'' , 1 which involved veterinarians, ethicists and animal scientists who presented on the scientific, social, political, market, and legal aspects of how and why animal welfare decisions are made. We want to develop and advocate for good evidence-based policies that will provide the right number of veterinarians, with the right skills, in the right places, to meet Australia''s need for veterinary services into the future. Some additional skills and experience that are useful include being a member of community organisations, being a member of other boards and committees, a commitment to animal health and welfare, and the ability to prepare reports for the AVA Board. The AVA has been working closely with the Australian Department of Agriculture and human health groups to join this global campaign to promote responsible use of antibiotics.
cord-014546-arw4saeh	2017	MERS-CoV was discovered in 2012 in the Middle East and human cases around the world have been carefully reported by the WHO. In 2015, MERS-CoV spread from the Middle East to South Korea which sustained an outbreak. In order to evaluate the relative order and significance of geographic places in spread of the virus, we generated a transmission graph (Figure 1) based on methods described in 1. Places with high betweenness represent key hubs for the spread of the disease. Most important among the places in the MERS-CoV epidemic is Saudi Arabia as measured by the betweenness metric applied to a changes in place mapped to a phylogenetic tree. Saudi Arabia is the source of virus for Jordan, England, Qatar, South Korea, UAE, Indiana, and Egypt. The United Arab Emirates has a bidirectional connection with Saudi Arabia indicating the virus has spread between the two countries. Phylogenetics; Transmission Graph; MERS-CoV; Syndromic; Genetic
cord-016451-k8m2xz0e	2020	Influenza, measles, SARS, MERS, and smallpox illnesses are caused by highly infectious viral pathogens that induce critical illness. Measles infects and disrupts tissues throughout the body; however, severe disease is primarily due to lower respiratory tract and neurological complications [72] . Global epidemiology of avian influenza A H5N1 virus infection in humans, 1997-2015: a systematic review of individual case data Transmission of Middle East respiratory syndrome coronavirus infections in healthcare settings Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection Viral RNA in blood as indicator of severe outcome in Middle East respiratory syndrome coronavirus infection Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection
cord-016842-sow7k53m	2017	Examining 103,133 news articles that are the most popular for different demographic groups in Daum News (the second most popular news portal in South Korea) during the whole year of 2015, we provided multi-level analyses of gender and age differences in news consumption. For this study, we collected and analyzed the daily top 30 news items for each gender (male and female) and age group (10s, 20s, 30s, 40s, and 50s) in Daum News, the second most popular news portal service in South Korea, for the entire year of 2015. We now quantify differences in news consumption across demographic groups in four dimensions: (1) by actual news item, (2) by section, (3) by topic, and (4) by subtopic. We look into news consumption at different levels and find that section and topic preferences are similar across groups, but subtopic preferences are not.
cord-018016-r7tg0s45	2019	This work deals with developing an application where users can interactively view information about the infection in the form of plots, tables and maps. By viewing the data visualizations, users can analyze MERS cases better, find trends, monitor the disease and help authorities set detection and prevention guidelines. In the case of different cases analysis, the user can view the information as pie charts and maps, or tables. The analysis based on all cases reported in "all cities within Riyadh region" during January to February 2019 is shown in Fig. 2 . The table also has provision for searching values and selecting the number Application page corresponding to "Different Cases Analysis" tab for cities within a region of records to be displayed in a page. In this paper, we have created an interactive visualization tool for MERS Co-V infection cases based on details of cases reported in Saudi Arabia.
cord-018239-n7axd9bq	2018	The following topics should be included in the travel advice consultation: 5 Vaccinations (general and country specific) 5 Country-specific diseases 5 Malaria prophylaxis 5 Mosquito prophylaxis (wearing bright long-sleeved clothes, avoiding perfume, staying in air-conditioned rooms, using a mosquito net, using insect repellents, staying inside at dawn and dusk) 5 Food consumption and drinking overseas (no consumption of ice cubes, uncooked meals, salads and food, which is exposed to flies, limited alcohol consumption) 5 UV protection (using sun cream, avoiding sun exposure between 11.00 and 15.00 o'' clock, remaining in shaded areas, wearing a hat and covering skin) 5 Fitness assessment for travelling, flying and diving 5 Challenges of different climates and their effects on the personal health (dehydration, hyperthermia) 5 Medications 5 Thrombosis counselling 5 Counselling on symptoms on return, which require review (fever, skin changes, abnormal bleeding, lymphadenopathy, diarrhoea) 5 Sexual transmitted diseases 5 Contraception 5 Rabies
cord-018438-1tkevj8v	2018	Specifically, we aim to study the disease dynamics in a heterogeneous population consisting of SS and NS individuals, and develop a deterministic model based on ordinary differential equations (ODEs) which is expanded to a stochastic model that is implemented as a continuous-time Markov chain (CTMC) system and approximated by a multitype branching process [1, 2] . In fact, the stochastic threshold (i.e., probability of a disease outbreak) is directly related to the basic reproduction number as defined in Table 3 State transitions and rates for the CTMC model with Poisson rates Similarly, we find that the time to outbreak-where an outbreak is defined as 50 or more people in all of the E, A, and I classes-is reduced when the initial infected individual in a simulated MERS or Ebola disease situation is an SS rather than an NS (Fig. 7a, c) .
cord-018504-qqsmn72u	2014	5. How would you partner with the local health-care system (i.e., community health centers, hospitals, physician practices) to assure that they are following CDC testing guidelines and to assist with consistent outreach and prevention education efforts? Some examples of how public health works to prevent additional illness include identifying close contacts to the infected person and recommending prophylaxis medication to prevent them from becoming ill (antibiotics, antivirals, vaccine, etc.), providing disease prevention recommendations (washing hands, covering cough, etc.), recognizing outbreaks, and identifying and controlling their source (healthcare-associated outbreaks, foodborne outbreaks, etc.). Further investigation by the New Hampshire Department of Health and Human Services (NHDHHS) revealed that the cause of the outbreak was drug diversion ("…the stealing of narcotic pain medication intended for patients for self use"; NHDHHS 2013, p.
cord-022046-q1exf47s	2018	Middle East respiratory syndrome (MERS) is an emerging infectious zoonotic disease caused by a novel coronavirus (CoV). 4 Surveillance of DCs in KSA has shown that MERS-CoV clade B has been enzootic in the camel population in Arabia Genetic deep sequencing methods (i.e., high-throughput sequencing) have been readily available to researchers since the disease was first reported. 8 Nevertheless, given the prevalence of MERS-CoV infection in the Middle East''s DC population and due to the potential for spillover to the human population in direct contact with DCs, the development of a vaccine for use in DCs may be feasible. Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia Detection of the Middle East respiratory syndrome coronavirus genome in an air sample originating from a camel barn owned by an infected patient
cord-024569-d9opzb6m	2019	Using two waves of online panel data collected at two different time points during the MERS crisis, I investigate how individuals'' traditional and social media use during the crisis produced various consequences, including increased MERS knowledge, negative emotions such as fear and anxiety, and direct and indirect facilitation of MERS preventive behaviors. I expected that both traditional and social media use in times of crisis could directly and indirectly facilitate preventive behaviors (via MERS knowledge) and negative emotional responses to the MERS situation. I also expect that traditional and social media use about the Korean MERS crisis stimulated negative emotional responses, which in turn influenced both precautionary and panic behaviors in media users. Using two sets of data collected at two different time points during the 2015 MERS crisis in Korea, I investigated how traditional and social media use influenced MERS knowledge, fear and anxiety about the MERS situation, and adoption of preventive behaviors.
cord-103046-w8bm4p44	2020	Multiple studies have examined the susceptibility of domestic animals to CoV-2 to establish the risk of zoonotic transmission and two studies have shown chickens and 24 Middle East Respiratory Syndrome coronavirus (MERS-CoV), another coronavirus of 26 high concern associated with zoonotic infection, was first detected in patients with severe acute 27 lower respiratory tract disease in Saudi Arabia in 2012. For MERS-CoV, dromedary 35 camels appear to be the primary natural reservoir of infection to humans, but other domestic 36 animals seem to be susceptible to infection (7, 8) . Because poultry are so widespread and have close and extended contact with humans, 39 and other mammals in many production systems, including live animal markets, susceptibility 40 were conducted with SARS-CoV-2 and MERS-CoV in five common poultry species. Susceptibility of ferrets, cats, 109 dogs, and other domesticated animals to SARS-coronavirus 2. Middle East Respiratory Syndrome (MERS), and SARS-114 Middle East 118 respiratory syndrome coronavirus infection in non-camelid domestic mammals.
cord-103739-mmkrwj8t	2020	Metabolic labelling of newly-synthesized viral RNA followed by quantitative EM autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs MERS-CoV and SARS-CoV, and the gamma-CoV infectious bronchitis virus. In infected cells, the CoV RNA-23 synthesizing machinery associates with modified endoplasmic reticulum membranes that are 24 transformed into the viral replication organelle (RO). In infected cells, the CoV RNA-23 synthesizing machinery associates with modified endoplasmic reticulum membranes that are 24 transformed into the viral replication organelle (RO). 106 double-membrane spherules (DMSs) 107 We first set out to analyse the ultrastructure of MERS-CoV-infected Huh7 cells under sample 108 preparation conditions favourable for autoradiography (see Materials and Methods) (Fig 1, S1 109 Video). Association of polioviral proteins of the P2 89 genomic region with the viral replication complex and virus-induced membrane synthesis as 90 visualized by electron microscopic immunocytochemistry and autoradiography
cord-103899-6tqm99g1	2020	Hence, analyzing the role of these types of nucleotides in antiviral immune responses and the characterization of miRNA target genes might contribute to understanding the mechanisms of the interplay between the host and viruses, and in the future, potentially result in discovering therapeutic strategies for the prevention and treatment of acute COVID-19 infection. This review will summarize the recent discoveries associated with miRNAs in various respiratory infections caused by viruses, especially coronavirus, and address all feasible therapeutic options to mitigate the burden of VRIs. The humoral immunity is immunologically categorized as an acquired immune response in which T helper cells collaborate with B cells to differentiate these types of cells to plasma cells [17] [18] [19] . The immune responses against VRIs, such as IV, hRV, human coronavirus (HcoV), hMPV, and RSV, are correlated with the aberrant expression of several miRNAs in epithelial cells and participate in the pathogenesis of chronic and acute forms of respiratory disorders (Table 1 ) [16] .
cord-104500-m0kfom0x	2020	A comprehensive search was conducted among literature available in multiple electronic sources to find articles that addressed the "potential role of SSEs on severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic" and were published before 20(th) of August 2020. Specific screening strategies within potential super spreading host groups can also help to efficiently manage severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) epidemics, in contrast to the partially effective general restriction measures. However, the respective potential impact of SSEs on SARS-COV-2 outbreak is composed and presented in the current review, thereby implying the warranted effort required for effective SSE preventive strategies, which may lead to overt global community health benefits. Following this initial selection stage, further screening was performed by all reviewers, using the previously described search items to identify parameters determining the global impact of COVID-19 due to SSEs. Identified parameters included the global impact of immunity and vaccination, the holy cup and religion transmission, and the austerity caused by COVID-19 and other coronavirus epidemics due to restrictions applied.
cord-227268-8k9zaqsy	2013	This gave rise to the theory that HIV is an SS epidemic; the candidates for the superpreaders are: (a) persons in the primary retroviral-infection period that lasts a few weeks, who have a thousand times the level of virus in blood and semen found in chronically-infected patients; and (b) cases like "patient zero," the Canadian airline attendant with an impressive Rolodex of sexual partners in many cities, described in ''Randy Shilts''s 1987 book, And the Band Played On. priate kind of model is called a "stochastic multi-type branching-process." The adjective "stochastic" refers to random events, as in a dice game; in computer terms, when simulating the model the program makes calls on the random number generator, abbreviated RNG (supplied with your operating system), when making updates.
cord-252049-rgdynmla	2015	
cord-252397-qlu7dilh	2015	Results from a natural history study of MERS-CoV-infected rhesus monkeys indicated that intratracheal inoculation induced a non-lethal disease with limited pathology observed in recovering animals at 28 days post-inoculation and infectious virus could be recovered from lung but not other tissues assayed (Yao et al., 2014) . One subject in the MERS-EMC inoculated group appeared to develop a secondary infection observed by CT that increased to study end, day 25 post-exposure. With the use of CT, we observed that IT inoculation of common marmosets with MERS-JOR or MERS-EMC isolates resulted in a non-lethal disease characterized by limited clinical signs and moderate consolidative lung pathology that did not completely resolve by study end. In this experiment, we sought to determine if there were virus specific differences in disease progression following intratracheal inoculation of common marmosets with Middle Eastern Respiratory Syndrome Coronavirus, commonly known as MERS-CoV, with two common laboratory viral isolates (MERS-EMC and MERS-Jordan).
cord-252456-971d0sir	2020	The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. Currently, the case fatality rate is relatively low (⁓3.6%) compared to infections with severe acute respiratory syndrome coronavirus (SARS-CoV, (10%) and MERS-CoV (32%) [11] . Based on the previous emergence history of SARS-CoV, the presence of a large number of mammals and birds overcrowded in one place may give a chance for pathogens, particularly those with RNA genomes such as coronaviruses and influenza viruses, to emerge. Based on the previous experience from the other emerging diseases, particularly SARS-CoV and influenza viruses, avoiding the mixing of various species of animals, birds, and mammals, is highly suggested [51, 65, 66] . The process of decontamination of the virus-contaminated surfaces by the appropriate disinfectants or virucidal agents was successful in case of other respiratory viruses such as SARS-CoV and avian influenza [59] .
cord-252600-bvh1o64r	2018	We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The structure-guided design of inhibitor (I) encompassed the following steps: (a) we first determined a high resolution X-ray crystal structure of MERS-CoV 3CLpro in complex with GC376 ( Fig. 2/Panel A) . Validation of this idea was obtained by synthesizing extended inhibitor GC813 and determining a high resolution X-ray crystal structure of the MERS-CoV 3CLpro:GC813 complex ( Fig. 2/Panel B) . More importantly, representative aldehyde bisulfite adduct compounds 10a and 10c display potent inhibition toward MERS-CoV in both enzyme and cell-based systems, with low cytotoxicity (CC 50 > 100 mM) ( Table 2 and Fig. 4 ).
cord-252883-1ub01j2x	2019	Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The first case of infection attributed to Middle East respiratory syndrome coronavirus (MERS-CoV) was detected in Saudi Arabia in June 2012 [1] . Despite these viruses being identified in several reports as causing lower respiratory tract infections, it was generally accepted that coronaviruses were of low pathogenicity until the emergence of SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) in 2002, a virus with a fatality rate estimated at 10%. Very shortly afterwards, in September 2012, a second patient was admitted to hospital in the United Kingdom for severe respiratory infection related to a novel coronavirus following travel to the Middle East. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission
cord-253077-61fmul8c	2020	Lastly, Nonhuman primate (NHP) studies and patient data on SARS-CoV-1 have also shown that virus spike-specific IgG responses can exacerbate acute lung injury due to repolarization of alveolar macrophages into pro-inflammatory phenotypes and enhanced recruitment of inflammatory monocyte via CCL2 and IL-8 (Clay et al., 2012; Liu et al., 2019) . Collectively, these data suggest that cross-talk with monocytes might impair NK cell recognition and killing of SARS-CoV-2infected cells, and antibodies targeting IL-6 and TNF-signaling may benefit enhanced NK cell functions in COVID-19 patients ( Figure 2 ). However, these CD4 T cells lacked phenotypic markers of activation and were specific for C-terminal S protein epitopes that are highly similar to endemic human coronaviruses, suggesting that crossreactive CD4 memory T cells in some populations (e.g., children and younger patients that experience a higher incidence of hCoV infections) may be recruited into an amplified primary SARS-CoV-2-specific response (Braun et al., 2020) .
cord-253238-ptmxkpae	2020	Furthermore, testing stool after a patient has been infected with COVID-19 may be necessary to monitor any GI complications, and the potential for fecal-oral transmission after respiratory symptoms has resolved. Despite the limited information on COVID-19 and its GI symptoms, information from SARS-CoV and MERS-CoV provides some insights on the symptoms and disease severity from other CoVs. The MERS-CoV has shown to infect human primary intestinal epithelial cells, small intestine It is also found to transmit via the fecal-oral route [35] . Physicians should monitor for GI symptoms in COVID-19-infected patients and examine whether the virus continues to remain in their stools after their respiratory symptoms have resolved. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus
cord-253337-xdexrlq3	2017	After the South Korea government recognized the outbreak of MERS in Daejeon, cohort quarantine (isolation of persons who had been in contact with patients with confirmed cases in the hospital ward) was applied. Epidemiologic investigators of the Korea Centers for Disease Control and Prevention started their outbreak investigation with face-to-face interviews of the index casepatient in Daejeon and the 25 additional case-patients with confirmed MERS-CoV infection. When we checked the closed-circuit television recordings from hospital A to estimate how many persons could have been in contact with the Daejeon index case-patient, we found that he had been in several sections of the hospital ward, in particular those located on the left side of the nurse station. Quarantine policy to prevent additional transmission of MERS, Daejeon, South Korea* Action  The cohort quarantine applied to admitted patients and their caregivers (professional or family) exposed to the MERS case-patients.
cord-254976-la9g6g5t	2016	PURPOSE: Emergency department (ED) nurses suffer from persistent stress after experiencing the traumatic event of exposure to Middle East respiratory syndrome coronavirus (MERS-CoV), which can subsequently lead to burnout. CONCLUSIONS: ED nurses taking care of MERS-CoV-infected patients should be aware that burnout is higher for nurses in their divisions than nurses in other hospital departments and that job stress is the biggest influential factor of burnout. The scale for measuring hospital resources for the treatment of MERS-CoV was developed by the researcher based on previous studies reporting material resources as one of the influencing factors of burnout [5, 9, 13, 14] . The participants'' general characteristics, MERS-CoV-related burnout, job stress, fear of MERS infection, available hospital resources for the treatment of MERS-CoV, and support from family and friends were analyzed with frequencies, percentages, means, and standard deviations.
cord-255339-oudj079q	2019	
cord-255378-qgklt8wa	2016	title: NMR assignments of the macro domain from Middle East respiratory syndrome coronavirus (MERS-CoV) The newly emerging human pathogen, Middle East respiratory syndrome coronavirus (MERS-CoV), contains a macro domain in the highly conserved N-terminal region of non-structural protein 3. In this study we report the preliminary structural analysis through solution NMR spectroscopy of the MERS-CoV macro domain. The near complete NMR assignments of MERS-CoV macro domain provide the basis for subsequent structural and biochemical investigation in the context of protein function. Secondary structure elements of MERS-CoV macro domain were identified by calculating the chemical shift deviations of the Ca(DdCa) and Cb(DdCb) from the random coil values and was corroborated by analysis of the chemical shift data using the program TALOS? Six helices and seven b-strands could be deduced for MERS-CoV moacro domain protein based on the secondary chemical shift analysis, which results in residues 21-27, 47-54.
cord-255488-nvgz53su	2019	An animal model that supports MERS-CoV infection and causes severe lung disease is useful to study pathogenesis and evaluate therapies and vaccines. To generate a mouse model with associated morbidity and mortality from respiratory disease, we serially passaged HCoV-EMC/2012 strain in the lungs of young hDPP4 KI mice. Alternative strategies for the creation of mouse models of MERS-CoV infection are generation of DPP4 humanized mice and adaptation of the virus to the animals. Similarly, our human DPP4 knock-in mouse model supported MERS-CoV replication but did not lead to a severe lung disease phenotype [33] . Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4 Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice
cord-255628-bm4nogig	2015	First reported in September, 2012, human infections with Middle East respiratory syndrome coronavirus (MERS-CoV) can result in severe respiratory disease, characterised by life-threatening pneumonia and renal failure. He was asymptomatic upon return to South Korea on May 4, but tested positive for MERS-CoV on May 20, along with two additional cases: his 64-year-old wife, and a 76-year-old male who was a fellow patient. MERS-CoV infection was confi rmed on May 29, marking the fi rst laboratoryconfirmed case in China (appendix), and the patient was immediately put in isolation. 6 In response, the Chinese health authorities promptly placed 38 high-risk contacts under surveillance, but it is not known whether additional contacts exist and further MERS-CoV infections in China remains a possibility. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients Middle East respiratory syndrome coronavirus (MERS-CoV)-Republic of Korea Middle East respiratory syndrome coronavirus (MERS-CoV)-China
cord-255815-5d9bqji0	2017	An orthogonal technique based on intrinsic tryptophan fluorescence also showed that MERS-CoV PL(pro) undergoes a single thermal transition and unfolds via a pathway of two-state folding with a T (m) value of 51.4 °C. In a similar experiment, MERS-CoV PL pro was gradually heated from 20 to 80°C at a rate of 1°C/min during which tryptophan fluorescence was measured by exciting at 295 nm and collecting at 330 and 350 nm to obtain the temperature melting curve. Commonly, protein unfolding fluorescence spectra are characterized by a long wavelength shift ''''red-shift.'''' But some proteins, Fig. 2 a Sequence of C-terminal His-tagged MERS-CoV PL pro showing ten Tyr and five Trp residues, which are highlighted in green and blue, respectively. Our result showed that the band intensity of the supernatant samples incubated from 20 to 70°C was apparently unchanged (Fig. 5) , indicating Fig. 3 Thermally induced structural changes in MERS-CoV PL pro as monitored by the intrinsic tryptophan fluorescence spectroscopy.
cord-255871-dau9tz6u	2015	BACKGROUND: It is crucial to understand the current status of clinical laboratory practices for the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infections in the Republic of Korea to be well prepared for future emerging infectious diseases. The number of MERS-CoV rRT-PCR tests performed was collected from 32 medical institutions and five referral medical laboratories. A total of 27,009 MERS-CoV rRT-PCR tests were performed at 32 medical institutions (N = 11,502) and five referral medical laboratories (N = 15,507) (Table 1 and Fig. 1 ). The proportion of medical institutions was significantly underestimated because one tertiary care hospital submitted responses for the survey but not the specimen list, and the numbers of MERS-CoV rRT-PCR tests and positive specimens at this institution would have been predominant in the reporting medical institutions. Table 2 shows the current status of clinical laboratories in medical institutions with respect to their response to the outbreak of MERS-CoV infections.
cord-256020-wrui3i2l	2020	The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease is caused by SARS-CoV-2, a zoonotic pathogen that acquired mutations as it crossed the species barrier from bat to pangolin enabling it to infect humans. 5 The clinical symptoms of COVID-19 include fever, cough, and pneumonia, which makes the disease enormously dangerous with a high case fatality rate. 11 Symptoms of human SARS-CoV-1 infections include headache, fever and respiratory complications such as cough, dyspnea, and pneumonia. 81 The main goal of SARS-CoV-2 diagnosis is to accurately detect the virus and to minimize further transmissions by timely isolation and treatment of infected patients. 112 This implies that variation in ACE-2 expression in COVID-19 patients is likely to affect susceptibility, symptoms and intervention outcomes following SARS-CoV-2 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations
cord-256086-8qfeoayb	2016	The Middle East Respiratory Syndrome (MERS) that was followed closely by major media outlets in the USA provides an opportunity to examine the relationship between exposure to public communication about epidemics and public awareness and knowledge about new risks. 2, 6, 7 One key importance is to study the association between social and individual factors and communication inequalities-differences among people from different socioeconomic positions (SEPs), racial, ethnic and geographical backgrounds, to understand how individuals access, interpret and act on messages they have received 1,5,8 -13 and to identify the best ways to quickly and effectively reach diverse populations with important preventive information. 24, 25 This lesson was reinforced by the experience of recent international pandemic outbreaks of diseases and viruses such as the SARS, avian flu and H1N1 when the constructs of strategic risk communication such as public awareness, media exposure and knowledge about specific threats were further identified and assessed.
cord-256300-emsvxxs5	2019	We review here our current understanding of the mechanism used by CoVs to infect host cells based on recent structural and biochemical studies of S glycoprotein ectodomains in prefusion and postfusion states as well as complexes with known receptors or neutralizing antibodies. Recent structural work comparing recombinant S proteins from SARS-CoV and MERS-CoV in isolation and in complex with their cognate receptors or neutralizing antibodies suggested an activation mechanism for coronavirus fusion (Gui et al., 2017; Kirchdoerfer et al., 2018; Song et al., 2018; Walls et al., 2019; Yuan et al., 2017) . Major antigenic determinants of MHV and SARS-CoV S overlap with the fusion peptide region (Daniel et al., 1993; Zhang et al., 2004) and binding of neutralizing antibodies to this site could putatively prevent fusogenic conformational changes, as proposed for influenza virus hemagglutinin or HIV envelope (Corti et al., 2011; Kong et al., 2016; Lang et al., 2017) .
cord-256537-axbyav1m	2016	In reviewing the new challenges posed by these emergent events, new technologies promise some answers; however, global health security against pandemic threats, particularly given the uneven distribution of global resources for prevention, detection, and response, remains a critical area of challenge. Specifically: (1) it is now well appreciated that influenza can migrate directly from avian sources to humans, and the appreciation of the actual directness of ''species jumping'' has moved forward; (2) new infections have also introduced uncertainty in transmission dynamics with emphasis on super-spreader events as well as nosocomial transmission; (3) infectious particles are not confined to those organisms which contain genetic material; (4) a new paradigm such as ''Planetary Health'' may be necessary for defining these trends; and (5) global preparedness and response is not in place for the next pandemic. To summarize, the recent episodes of respiratory infectious diseases related to influenza, SARS-CoV, and MERS-CoV have demonstrated increasingly direct links between animal and human infections, agile intercontinental geographic spread, and complex transmission dynamics including ''superspreader'' events.
cord-256750-5m7psxri	2020	Acute infectious outbreaks of Emerging Infectious Diseases (EIDs) are known to influence the physical as well as the mental health of affected patients, as observed during similar events such as the Severe Acute Respiratory Syndrome (SARS) outbreak [3] , which was associated with such issues during the acute phase [4] and the long-term follow-up phase [5, 6] . Thus, the present study explored mental health issues and related factors in MERS survivors 12 months after the outbreak to determine the long-term psychological outcomes of this population. The univariate analysis revealed that several factors were significantly associated with PTSD, including previous psychiatry history, having a family member who died from MERS, depression and anxiety during the MERSaffected period, greater perceived stigma currently and during the illness, and negative coping strategies (Table S2) . Our study showed that nearly half the assessed MERS survivors experienced significant mental health problems, including PTSD and depression, at 12 months post-MERS.
cord-256784-wfaqim7d	2016	Middle East Respiratory Syndrome (MERS-CoV) was first isolated in September 2012 from a patient in Saudi Arabia who presented two months earlier with severe acute respiratory infection and acute renal failure [1] . Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines Effects of human anti-spike protein receptor binding domain antibodies on severe acute respiratory syndrome coronavirus neutralization escape and fitness Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vector-based vaccines carrying the spike protein of Middle East respiratory syndrome coronavirus Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies
cord-256806-g42n51n9	2019	title: Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014–2017 Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Our study aimed to identify risk factors for MERS-CoV seropositivity among live-animal market and slaughterhouse workers. The survey consisted of questions covering worker demographics; occupational history; contact with various animal species; travel history; medical history; consumption of raw camel milk, raw camel meat, and camel urine; specific tasks performed with camels; types of personal protective equipment (PPE) worn; and handwashing practices (Appendix 1, https://wwwnc.cdc.gov/EID/article/25/5/18-1728-App1.pdf). Our study investigated risk factors for MERS-CoV seropositivity in animal market and slaughterhouse workers at a site previously associated with zoonotic transmission of MERS-CoV. Among market workers, handling live camels and either administering medications to camels or cleaning equipment were practices associated with significantly increased risk for MERS-CoV seropositivity.
cord-257511-4ftedh1a	2018	Knockdown of endogenous two-pore channels (TPCs), targets for the Ca2+ mobilizing second messenger NAADP, impaired infectivity in a MERS-CoV spike pseudovirus particle translocation assay. This inhibitory effect was dependent on appropriate subcellular targeting of the active channel as overexpression of a functional TPC2 channel rerouted from acidic Ca 2+ stores to the cell surface (TPC2pm, [25] ) by deletion of the NH 2 -terminal lysosomal targeting motif did not inhibit MERS-CoV pseudovirus infectivity (Fig. 2A) . To examine the effects of TPC regulators on MERS-CoV pseudovirus translocation, a fixed concentration (10μM) primary drug screen was performed in Huh7 cells, with the goal of identifying plasma membrane-permeable compounds with inhibitory activity on MERS-CoV pseudovirus translocation. Addition of the PIKfyve inhibitor YM201636 to reduce PI(3,5)P 2 levels, a phosphoinositide which activates TPC channels, decreased MERS-CoV pseudovirus translocation ( Supplementary Fig. 6 A&B) .
cord-257587-xjoyrdhj	2018	Here, we have performed a pilot screen for novel modulators of NAADP-sensitive Ca 2+ release in the sea urchin egg homogenate system and assessed tractability of the resulting ''hits'' against both endogenous NAADP-evoked Ca 2+ responses and a pseudotyped MERS-CoV translocation assay in human cell lines [25] . Fangchinoline, an inhibitor of NAADPevoked Ca 2+ signals and MERS pseudovirus translocation in a human cell line [25] , decreased the magnitude of NAADP-evoked Ca 2+ release (peak amplitude 47 ± 2% of control response, blue traces in Fig. 1A ) with lesser effects on the size of IP 3 or cADPR-evoked Ca 2+ transients (Fig. 1A) . These final activities (steps ''3'' and ''4'') encompassed: (i) counter-screening for more generalized actions against acidic Ca 2+ stores, for example lysosomotropism [28, 29] , (ii) quantifying effects on NAADP-evoked Ca 2+ signals evoked by single cell microinjection of NAADP, and (iii) correlating effects on Ca 2+ release with bioactivities in the MERS pseudovirus translocation assay.
cord-258032-buh1e4tm	2017	In this paper, a class of novel four-dimensional dynamic model describing the infection of MERS-CoV is given, and then global stability of the equilibria of the model is discussed. It is well-known that dynamic models are still playing important roles in describing the interactions among uninfected cells, free viruses, and immune responses (see, e.g., [4] [5] [6] [7] ). Based on basic dynamic model (1) and Figure 1 , we propose the following novel four-dimensional dynamic model which describes the spread of the MERS-CoV and the expression of DPP4:̇= The basic reproductive ratio of the virus for model (2) is (2) always has an infection-free equilibrium 0 = ( 0 , 0, 0, 0 ) = ( / , 0, 0, 1 / ). Figure 2(a) shows the trajectory of model (2) with suitable initial condition, which shows that the infection-free equilibrium 0 is asymptotically stable.
cord-258281-gxwk8jq9	2020	Based on recently published literature and official documents, this review provides an introduction to the pathogenesis, pathology, and clinical features of COVID-19 and has focused on the current researches on clinical features, pregnancy outcomes and placental histopathological analysis from pregnant women infected with SARS-CoV-2 in comparison with SARS-CoV and MERS-CoV. Although there is no unequivocal evidence to support the fetal infection by intrauterine vertical transmission of SARS, MERS and SARS-CoV-2 so far, more and more articles began to report maternal deaths due to COVID-19. There were no cases of vertical transmission identified among pregnant women infected with SARS 44-49 so far, but SARS during pregnancy is associated with high incidences of spontaneous miscarriage, preterm delivery, intrauterine growth restriction, endotracheal intubation and admission to the neonatal intensive care unit [44] [45] [46] . This is a review on pregnant women infected by SARS-CoV-2, SARS, and MERS, including their pathogenesis, clinical manifestations and pregnancy outcomes. Middle East respiratory syndrome coronavirus (MERS-CoV) infection during pregnancy: report of two cases & review of the literature
cord-258323-vdeffy4l	2019	
cord-258611-uzzs8w1j	2017	BACKGROUND: There is global health concern that the mass movement of pilgrims to and from Mecca annually could contribute to the international spread of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). DISCUSSION AND CONCLUSION: The MERS-CoV and respiratory viruses detection results at points of entry in China from 2013 to 2015 indicated that there were no MERS-CoV infection but a 5.7% positive influenza viruses in returning Chinese pilgrims. As of November 2015, there had been 1618 laboratoryconfirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection reported to the World Health Organization, and at least 579 cases had died [1, 2] . Two hypotheses were tested: (1) There is a significant difference in the positive and negative rates of influenza virus detection between Hajj pilgrims with symptoms and those without. In this study, we did not detect any cases of MERS-CoV infection but respiratory virus infections including influenza A and B, hMPV, hRSV, and human coronavirus were detected among Hajj pilgrims returning to China.
cord-258892-1xmoeoyh	2014	Enhanced surveillance involved the collection of a minimum dataset for each possible case, including demographic data, clinical symptoms, travel and contact history, and results of testing for respiratory pathogens (6) . In addition to testing the 77 persons who met all of the possible case criteria, MERS-CoV testing was conducted on 13 patients who had severe acute respiratory disease but did not meet the travel requirements: 2 had a travel history outside the Middle East, 4 had no travel history in the relevant exposure period, and travel histories of the remaining 7 were unknown. This report on the characteristics of patients traveling to England from the Middle East and tested for MERS-CoV enables a first crude estimation of the positive predictive value of different signs and symptoms during the first year following the emergence of this pathogen.
cord-259051-6kuh4njb	2019	title: MERS-CoV infection among healthcare workers and risk factors for death: Retrospective analysis of all laboratory-confirmed cases reported to WHO from 2012 to 2 June 2018 BACKGROUND: Approximately half of the reported laboratory-confirmed infections of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. This study aimed to describe secondary cases of MERS-CoV infection among healthcare workers and to identify risk factors for death. METHODS: A retrospective analysis was conducted on epidemiological data of laboratory-confirmed MERS-CoV cases reported to the World Health Organization from September 2012 to 2 June 2018. In this study, we use the epidemiological data of all MERS cases reported to date to WHO to describe secondary cases of MERS-CoV infection among healthcare workers and to identify the risk factors for death among healthcare workers with secondary infection.
cord-259200-65b267ic	2020	Subsequent to the severe acute respiratory syndrome (SARS) outbreak in China 2003, and the Middle East respiratory syndrome (MERS) outbreak in the Middle East in 2012, global concerns regarding the pathogenicity and epidemic/pandemic potential of novel human coronaviruses began to emerge, with some experts predicting that novel coronaviruses could likely again cross the species barrier and present humans with future pandemic-potential infections. 2019-nCoV is the seventh coronavirus species that is now known to infect humans, is also zoonotic in origin, and is the causative organism for the current viral pneumonia epidemic in China. The complete ban on market trading and sale of wild game meat in China on January 26th, 2020 will help prevent zoonotic transmission of 2019-nCoV in the current epidemic and, to a certain degree, help prevent emergence of new zoonotic infections.
cord-259347-3acsko74	2020	A new strain of human coronaviruses (hCoVs), Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been identified to be responsible for the current outbreak of the coronavirus disease 2019 (COVID-19). Data from multiple hACE2 transgenic mouse models has revealed that SARS-CoV detection in the brain is significantly delayed compared to that within the lung, consistent with the initial establishment of infection within the respiratory system before dissemination to the CNS [21À23]. In addition, the detection of SARS-CoV in CSF of patients with neurological manifestation has also provided direct evidence for the neuroinvasion and neurovirulence of hCoVs. However, the role of the virus in the process of the disease in acute phase as well as in the long term still remains elusive. Severe acute respiratory syndrome coronavirus infection of mice transgenic for the human Angiotensin-converting enzyme 2 virus receptor
cord-259374-m7q1roay	2019	Here, we demonstrate that NHC inhibits both murine hepatitis virus (MHV) (50% effective concentration [EC(50)] = 0.17 μM) and Middle East respiratory syndrome CoV (MERS-CoV) (EC(50) = 0.56 μM) with minimal cytotoxicity. Here, we demonstrate the potent antiviral activity of a broad-spectrum ribonucleoside analogue, β-d-N(4)-hydroxycytidine (NHC), against two divergent CoVs. Viral proofreading activity does not markedly impact sensitivity to NHC inhibition, suggesting a novel interaction between a nucleoside analogue inhibitor and the CoV replicase. To directly test the effect of NHC treatment on the mutational burden, we treated WT MHV with increasing concentrations of NHC and performed full-genome next-generation sequencing (NGS) on viral populations released after a single round of infection. Our results indicate that NHC decreases the titers of both WT and ExoN(Ϫ) MHV in a dose-dependent manner but that ExoN(Ϫ) MHV demonstrates a statistically Passage in the presence of NHC yields low-level resistance associated with multiple transition mutations.
cord-259443-5sv3dwbs	2016	title: Risk factors for severity and mortality in patients with MERS-CoV: Analysis of publicly available data from Saudi Arabia Initially, only limited information such as patients'' age, sex, nationality, address, date of diagnosis, presenting symptoms, and presence of any pre-existing condition were made publicly available; however, since 24 th September 2014, additional information on likely exposure to animals and other suspected MERS cases were added, and it was recorded whether the exposure likely occurred at health care settings or in community settings. In our study, presence of a respiratory disease was not a significant risk factor and we did not explore the association of older age with mortality, because essentially all patients aged ≥ 65 years in our cohort had a pre-existing disease, but age itself could be an independent risk factor, as other studies from Saudi Arabia and South Korea demonstrated that age > 60 years (in some studies ≥ 65 years) was significantly associated with mortality (Feikin et al., 2015; Majumder et al., 2015; Saad et al., 2014) .
cord-259658-rgrt6e6r	2019	To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC–MS)-based lipidomics approach. Importantly, supplement of additional LA and AA to coronavirus-infected cells significantly inhibited virus replication of both HCoV-229E and the highly virulent MERS-CoV, suggesting that the LA-AA metabolism axis is a common and essential pathway that could modulate coronavirus replication. To investigate how coronavirus perturbs host lipid metabolism, we performed lipidomics analysis on HCoV-229E-infected Huh7 cells and compared the results with those of the mock-infected cells. Therefore, combining pathway analysis and the authentic standards verification results, our data suggested that the LA-AA metabolism axis was the most significantly perturbed pathway and might be associated with lipids rearrangement or other processes in HCoV-229E infection.
cord-259703-9ef3u2mz	2015	T he Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized as a new febrile respiratory illness in Saudi Arabia in June 2012. Middle East respiratory syndrome coronavirus (MERS-CoV) -Saudi Arabia: Disease outbreak news Family cluster of Middle East respiratory syndrome coronavirus infections Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: A nationwide, cross-sectional, serological study Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: A report of nosocomial transmission Association of higher MERS-CoV virus load with severe disease and death, Saudi Arabia Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection Clinical management of severe acute respiratory infection when Middle East respiratory syndrome coronavirus (MERS-CoV) infection is suspected -Interim guidance Repurposing of clinically developed drugs for treatment of middle East respiratory syndrome coronavirus infection Infection Prevention and Control Recommendations for Hospitalized Patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV).
cord-260024-yrhlg6wm	2015	The Korea Centers for Disease Control and Prevention (KCDC) under the Ministry of Health and Welfare (MW) insisted on not sharing MERS information from the hospitals with the public at the initial stage of the outbreak under the pretext of hospital protection, although in reality this decision may have been based on nepotism. Considering that the MERS outbreak was not only a health issue but also an emergency management issue, the model for controlling similar epidemics or pandemics in the future-oriented model should involve all stakeholders in an early and co-ordinated response. Although many stakeholders tried to play their own roles during the MERS outbreak in Korea, their responses were somewhat late and unco-ordinated, and thus contributed to the national crisis. The key tenet is that Korea must not consider the MERS outbreak to be a hospital infection control issue.
cord-260334-xo8ruswo	2019	Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV. We have used this transduced mouse model to test the capacity of the antiserum derived from the dual route immunisation to neutralise MERS-CoV in vivo, by passive transfer prior to challenge with the EMC2012 strain and we have demonstrated a significant reduction in viral load in lung tissue in transduced mice.
cord-260420-4s7akmdp	2019	There is a need to enhance the knowledge translation for researchers, stakeholders, and private partners to support a growing network of individuals and agencies to achieve common goals to mitigate interand intra-species pathogen transmission via bioaerosols. New developments have enabled progress in this domain, and one of the major turning points has been the recognition that cross-disciplinary collaborations across spheres of human and animal health, microbiology, biophysics, engineering, aerobiology, infection control, public health, occupational health, and industrial hygiene are essential. There is a need to enhance the knowledge translation for researchers, stakeholders, and private partners to support a growing network of individuals and agencies to achieve common goals to mitigate inter-and intra-species pathogen transmission via bioaerosols. A network approach has proven successful in other cross-disciplinary fields, including One Health and eco-health whereby wildlife, computational and evolutionary biologists, microbiologists, virologists, epidemiologists, ecologists, environmental scientists, climatologists, and human, animal, and public health practitioners are collaborating to address challenges in zoonotic diseases research and control (17, 18) .
cord-260518-mswb3q67	2016	Since the Kingdom of Saudi Arabia is host to millions of pilgrims each year travelling from all continents, 29 tackling the threat of MERS and other infectious diseases with epidemic potential will require enhanced closer cooperation between those who provide human health, animal health, and environmental health services, locally, nationally, regionally, and internationally: the Middle Eastern, European, African, Asian, and American governments, veterinary groups, the WHO, the Food and Agriculture Organization (FAO), the African Union, the United Nations International Children''s Emergency Fund (UNICEF), The World Bank, Office International des Epizooties (OIE), CDC, Public Health England, the newly formed Africa CDC, and funding agencies among others. The persistence of MERS-CoV 4 years since its first discovery has created major opportunities for each of the Middle Eastern and African countries to take leadership of the ''One Health'' approach with a view to bringing this under regional and global umbrellas, to tackle new emerging and re-emerging infectious diseases with epidemic potential.
cord-261041-nrmj1qre	2019	However, using live virus-based MN assay might require working under high containment facilities especially when dealing with high-risk pathogens such as the Middle East respiratory syndrome-coronavirus (MERS-CoV). 5. Next day, change the media by removing old media and add 2 mL or 5 mL of fresh pre-warmed M-2 into a T25 or T175 tissue culture flask, respectively. 3. Seed 1 Â 10 4 Vero E6 cells (100 μL) per well into sterile 96-well tissue culture plate so that they are 90-95% confluent the next day (see Note 8). 3. Seed 1 Â 10 4 Vero E6 cells (100 μL) per well into sterile 96-well tissue culture plate so that they are 90-95% confluent the next day (see Note 8). Remove the 96-well tissue culture plate containing confluent Vero E6 cells and aspirate the media (see Note 15) .
cord-261163-n9tp9nx7	2017	
cord-261421-k1s5iy3u	2015	To assess the temporal dynamics of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels, specimens were collected at 1–2 month intervals from 2 independent groups of animals during April 2013–May 2014 in Al-Ahsa Province, Saudi Arabia, and tested for MERS-CoV RNA by reverse transcription PCR. Furthermore, MERS-CoV infection in dromedary camels was definitively proven by the detection of virus and virus sequences in respiratory specimens, feces, and milk collected from camels in Qatar (9, 13) , Oman (14) , Saudi Arabia (5, 15, 16) , and Egypt (17) . To address these limitations and to clarify the dynamics of MERS-CoV infection in these animals, we conducted a year-round study in which we collected a large number of specimens from the upper respiratory tracts of live dromedary camels and from the lungs of dromedary camel carcasses. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia
cord-261533-73721b24	2020	We therefore aimed to test peripheral blood mononuclear cells (PBMC) in workers from an abattoir in Kano, Nigeria, for MERS-CoV-specific T-cell responses to understand if the dromedary-exposed individuals in Africa have been infected by MERS-CoV. Evidence before this study Middle East respiratory syndrome coronavirus (MERS-CoV) is recognised as one of eight emerging pathogens of greatest threat to global public health, and dromedary camels are the source of human zoonotic infection. Because there was evidence that serological assays for MERS-CoV had suboptimal sensitivity for past infection and because we had previous data showing that T-cell assays for MERS-CoV are specific and potentially more sensitive than antibody detection, we investigated T-cell responses in dromedary-exposed abattoir workers and controls in Nigeria. 61 (53%) of the 115 participants had PBMCs available for additional testing for four endemic human coronaviruses (229E, HKU1, NL63, and OC43), including 18 dromedary-exposed workers positive and ten negative for a MERS-CoV T-cell response and 33 from the negative control groups who were all MERS-CoV T-cell negative.
cord-261566-fn08b0y2	2020	
cord-261876-7rsc803x	2020	
cord-262045-r2iqpmmc	2014	RESULTS: A reverse-transcription PCR assay for MERS-CoV targeting a 615 bp spike fragment provides a phylogenetic clustering of MERS-CoV variants comparable to that of full-length genomes. In addition, the MERS-CoV variant typing assay was performed on camel samples from a slaughterhouse in Qatar [13] and sequences for 14 MERS-CoV positive animals with cycle threshold values ranging from 12.9 to 32.2 as determined by UpE real time RT-PCR [17, 18] were obtained (Fig. 2) . Subsequent analyses revealed a region in the open reading frame that encodes the spike protein with a number of positions in which nucleotide variation occurs between MERS-CoV variants with a strong phylogenetic signal regarding previously identified clusters of viruses based on full-length MERS-CoV genomes. Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia
cord-262542-vevsgkp6	2017	title: ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. Here, we report development of MERS-CoV vaccine candidates that are based on two different viral vectors: Chimpanzee Adenovirus, Oxford University #1 (ChAdOx1) [26] and Modified Vaccinia virus Ankara (MVA) [27, 28] . Previously, we reported the ability of the strong early F11 promoter to enhance cellular immunogenicity of vaccine antigen candidates for malaria and influenza, as compared to utilising p7.5 or mH5 early/late promoters which resulted in a lower level of gene expression immediately after virus infection of target cells, but higher levels at a later stage [31] .
cord-262673-j2ot35lt	2020	Furthermore, respiratory epithelial cells and lung macrophages are capable of secreting a broad range of chemokines like IL-8, Macrophage inflammatory protein-1 (MIP-1), RANTES and cytokines including TNF-α, IL-6, IL-1β that influence the types of immune cells being recruited to the area in response to acute viral infections (177, 178) . Both Influenza and SARS virus can induce acute lung injury (ALI) which is accompanied by high levels of C5a, leading to the influx and activation of innate immune cells (199) (Figure 1) . Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus Middle East respiratory syndrome coronavirus shows poor replication but significant induction of antiviral responses in human monocytederived macrophages and dendritic cells Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells
cord-263016-28znb322	2015	
cord-263042-qdmunb9l	2016	
cord-263391-18x4ann5	2019	S ince the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 (1), more than 2,250 laboratory-confirmed cases have been reported to the World Health Organization (WHO); approximately one third of these cases were fatal. The Ministry of Health, Oman; Ministry of Health, Saudi Arabia; and Korea National Institute of Health, South Korea, donated convalescent serum and plasma samples from PCR-confirmed MERS-CoV-infected patients. We included MERS-CoV-negative serum with antibodies against other human coronavirus HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 (samples 3, 6, 7, 8, 13, 15, and 17) to test specificity of the assays ( Table 2 ). Participants detected pool A, the high-titer MERS-CoV antibody pool (sample 16) in all assays (Table 3) . The low-positive pool (pool C, sample 14) was only detected as positive in a single assay in the study, the Alpha Diagnostic International MERS NP ELISA performed in laboratory 05.
cord-263508-row2mn17	2013	Ten years after the devastating epidemic of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV), which resulted in a total of 774 deaths among more than 8000 confirmed cases in over 30 countries, the world is facing a new challenge posted by a "SARS-like" infection caused by another novel coronavirus emerging from the Middle East, which was originally named human coronavirus EMC/2012 (HCoV-EMC) and recently renamed by the Coronavirus Study Group of the International Committee for Taxonomy of Viruses as Middle East respiratory syndrome coronavirus (MERS-CoV). 6,7,10e14 Although the number of laboratory-confirmed cases remains limited, the severe clinical manifestations with an unusually high mortality rate of over 50%, the spread of the infection beyond the geographical confinement in the Middle East, and the epidemiological evidence of human-to-human transmission arising from the recent clusters of cases in a family in the United Kingdom (Cases 10 to 12), and in hospitals in KSA (Cases 18 to 30, 32 and 33) and France (Cases 31 and 34), have raised significant concerns on the possible emergence of another SARS-like epidemic in the near future.
cord-264199-8skyagsz	2014	title: Emerging respiratory infections: influenza, MERS-CoV, and extensively drug-resistant tuberculosis New research on the eff ectiveness of neuraminidase inhibitors to reduce mortality in patients admitted to hospital with infl uenza A H1N1pdm09 has been encouraging. 6 Although the eff ectiveness of antivirals to reduce mortality would ideally be derived from randomised controlled trials, a recent meta-analysis of trials was only able to collect data for fi ve reported deaths, only one of which was due to a respiratory cause. Using whole genome sequencing of 1000 prospectively collected tuberculosis isolates from patients in Russia, Casali and colleagues 8 provided evidence against the theory that acquiring drug resistance typically comes with a fi tness cost and reduced transmissibility. Eff ectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with infl uenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data
cord-264267-weat0qs6	2020	
cord-264408-vk4lt83x	2017	Well-developed animal models are necessary to understand disease progression, pathogenesis, and immunologic responses to viral infections in humans. NHPs including marmosets, cotton-top tamarins, and rhesus macaques infected with Norwalk virus are monitored for the extent of viral shedding; however, no clinical disease is observed in these models. Intracerebral and IN routes of infection resulted in a fatal disease that was highly dependent on dose while intradermal (ID) and subQ inoculations caused only 50% fatality in mice regardless of the amount of virus (liu et al., 1970) . Ferrets infected with Hendra or Nipah virus display the same clinical disease as seen in the hamster model and human cases (Bossart et al., 2009; Pallister et al., 2011) . Characterization studies with IFNAr −/− mice challenged with different routes (IP, IN, IM, and subQ) showed that CCHFV causes acute disease with high viral loads, pathology in liver and lymphoid tissues, increased proinflammatory response, severe thrombocytopenia, coagulopathy, and death, all of which are characteristics of human disease .
cord-264653-ms6zrrnd	2020	In view of the earlier evidence about effectiveness of repurposed lopinavir/ritonavir against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as preliminary docking studies conducted by the ICMR-National Institute of Virology, Pune, the Central Drugs Standard Control Organization approved the restricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients detected in the country. Hospitalized adult patients with laboratory-confirmed SARS-CoV-2 infection with any one of the following criteria will be eligible to receive lopinavir/ritonavir for 14 days after obtaining written informed consent: (i) respiratory distress with respiratory rate ≥22/min or SpO(2) of <94 per cent; (ii) lung parenchymal infiltrates on chest X-ray; (iii) hypotension defined as systolic blood pressure <90 mmHg or need for vasopressor/inotropic medication; (iv) new-onset organ dysfunction; and (v) high-risk groups age >60 yr, diabetes mellitus, renal failure, chronic lung disease and immunocompromised persons.
cord-264901-w285on4x	2019	
cord-264956-wbi0ird5	2018	An important lesson was learned from the world''s largest Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks that occurred in Saudi Arabia and South Korea: that health care-associated infection is a major cause of rapid pathogen spread in health care settings with a high risk of cluster infections. 12, 13 A valid risk-predictive model for MERS-CoV infection in dialysis patients may increase the likelihood of early virus detection. The authors attempt to develop an algorithm that combines demographic, clinical, radiological, and laboratory data to assess the early risk of MERS-CoV infection in dialysis patients who are suspected of having MERS-CoV infection and were diagnosed by real-time reverse transcription-PCR (rRT-PCR) between September 2012 and June 2016. This is the first study to develop a risk-prediction model in dialysis patients who screened for MERS-CoV infection by rRT-PCR. The model accurately predicts high-risk of MERS-CoV infection in dialysis patients.
cord-265128-i0d4lxko	2020	Among coronaviruses, the main protease (M(pro)) is an essential drug target which, along with papain-like proteases catalyzes the processing of polyproteins translated from viral RNA and recognizes specific cleavage sites. The present study is aimed at the identification of promising lead molecules for SARS-CoV-2 M(pro) enzyme through virtual screening of antiviral compounds from plants. The binding affinity of selected small drug-like molecules to SARS-CoV-2 M(pro), SARS-CoV M(pro) and MERS-CoV M(pro) were studied using molecular docking. Structure-based drug design primarily relies on molecular docking to identify lead molecules against the target proteins from chemical libraries [12, 13] . The natural products such as traditional medicines and plant-derived compounds (phytochemicals) are the rich sources of promising antiviral drugs [14] . The binding energies and inhibition constants of the phytochemicals with the SARS-CoV-2 M pro enzyme were compared with that of a set of twelve FDA approved antiviral drugs-a) Viral 
cord-265279-0zjpqnqp	2016	
cord-265282-v3n9ff16	2018	For the SIQ based ordinary differential equation (ODE) model, we perform the task of parameter estimation, and apply optimal control theory to the controlled SIQ model, with the goal of minimizing the infectious compartment population and the cost of implementing the quarantine and isolation strategies. Simulation results show that the proposed SIQ model can explain the observed data for the confirmed cases and the quarantined cases in the MERS outbreak very well, and the number of the MERS cases can be controlled reasonably well via the optimal control approach. Simulation results show that the proposed SIQ model can explain the observed data for the confirmed cases and the quarantined cases in the MERS outbreak very well, and the number of the MERS cases can be controlled reasonably well via the optimal control approach.
cord-265380-2gs34xcw	2019	
cord-265666-27ckjl7w	2018	RESULTS: The following 4 major themes emerged: "experiencing burnout owing to the heavy workload," "relying on personal protective equipment for safety," "being busy with catching up with the new guidelines related to Middle East respiratory syndrome," and "caring for suspected or infected patients with caution." Participants experienced burnout because of the high volume of work and expressed safety concerns about being infected. CONCLUSION: This study showed that creating a supportive and safe work environment is essential by ensuring adequate nurse staffing, supplying best‐quality personal protective equipment, and improving communication to provide the quality of care during infection outbreak. The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: An observational study
cord-265769-96p07nyz	2020	
cord-266031-tlrsco40	2020	
cord-266253-oyid5haj	2014	
cord-266260-t02jngq0	2019	
cord-266313-b518n9dx	2020	China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). When we set our sights on the broad-spectrum antiviral drugs, we found that a drug unlisted, remdesivir, has demonstrated strength in trials related to MERS-CoV and Ebola virus infection. This article starts from the structure, immunogenicity, and pathogenesis of infection of the SARS-CoV-2, and then analyzes the feasibility of conducting trials and putting into clinical use of COVID-19 from the pharmacological characteristics and successful cases of remdesivir. Remdesivir (GS-5734) is a nucleoside analogues drug (Fig. 3B ) with extensive antiviral activity and effective treatment of lethal Ebola and Nipah virus infections in nonhuman primates [21] . The need of treatment on COVID-19 is urgent, so if the results of clinical trials prove it has the potential to benefit the treatment, according to China''s "Compassionate Use", remdesivir will be more immediately used in patients with severe illness.
cord-266464-wuf3s8m0	2016	title: Viral RNA in Blood as Indicator of Severe Outcome in Middle East Respiratory Syndrome Coronavirus Infection We evaluated the diagnostic and clinical usefulness of blood specimens to detect Middle East respiratory syndrome coronavirus infection in 21 patients from the 2015 outbreak in South Korea. Respiratory specimens are preferred for viral RNA detection and confirmatory diagnosis of MERS-CoV infection in humans (5) . Our study aimed to evaluate the diagnostic utility of blood specimens for MERS-CoV infection by using large numbers of patients with a single viral origin and to determine the relationship between blood viral detection and clinical characteristics. Between the blood viral RNA-positive and -negative groups, we found no differences in age, duration from symptom onset to diagnosis of MERS-CoV infection, or an invasive procedure before the specimens were obtained (online Technical Appendix Table 3 ). Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission
cord-266987-ikt8r2o1	2020	The laboratory diagnostic methods for human coronavirus infections have evolved substantially, with the development of novel assays as well as the availability of updated tests for emerging ones. It must be appreciated that no matter how accurate and fast laboratory testing methods are, the diagnosis of viral pneumonias such as caused by SARS-CoV-2 involves collecting the correct specimen from the patient at the right time. The authors recommended to use serology to facilitate the diagnosis of SARS-CoV-2 infections when an NP swab specimen was collected inappropriately and the molecular assays were performed unsatisfactorily [42] . Several RT-PCR protocols for detection of SARS-CoV-2 RNA have been posted by the World Health Organization at https://www.who.int/emergencies/ diseases/novel-coronavirus-2019/technical-guidance/ laboratory-guidance. Considering the increased levels of mortality and infectivity associated with three novel-coronavirus outbreaks, these random-access, safe and simple tests, which offer fast and accurate detection and identification, are likely to have an immediate impact on prompt clinical and epidemiological decisions [7, 63] .
cord-267001-csgmc155	2020	
cord-267090-jc1k3fki	2019	
cord-267333-8b7hvorz	2014	
cord-267540-9p4rky4c	2015	
cord-268388-kkhuzf3p	2014	
cord-268483-joiajgs4	2020	
cord-268943-arjtjy53	2014	
cord-269386-bnh65bqg	2017	
cord-269437-0pvqvhqs	2013	CDC continues to work in consultation with the World Health Organization (WHO) and other partners to better understand the public health risk posed by the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), formerly known as novel coronavirus, which was first reported to cause human infection in September 2012 (1) (2) (3) (4) . CDC continues to work in consultation with the World Health Organization (WHO) and other partners to better understand the public health risk posed by the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), formerly known as novel coronavirus, which was first reported to cause human infection in September 2012 (1) (2) (3) (4) . Eight clusters (42 cases) have been reported by six countries (France, Italy, Jordan, Saudi Arabia, Tunisia, and the UK) (5) among close contacts or in health-care settings and provide clear evidence of human-to-human transmission of MERS-CoV. Persons who develop severe acute lower respiratory illness within 14 days after traveling from the Arabian Peninsula or neighboring countries should be evaluated according to current guidelines (available at http://www.cdc.gov/coronavirus/mers/case-def.
cord-269885-r8molh8c	2017	We report the first case of MERS-CoV infection during pregnancy occurred outside of the Middle East. We experienced a case of a Korean pregnant woman who was confirmed for a MERS-CoV infection via a polymerase chain reaction (PCR) test. Unlike other cases, this case is not only the first MERS-CoV infection during pregnancy occurred outside of the Middle East, but also the first case of MERS confirmed on 3rd trimester of pregnancy showing good outcome of both mother and baby. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling Interim infection prevention and control recommendations for hospitalized patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Impact of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) on pregnancy and perinatal outcome Middle East Respiratory Syndrome Coronavirus infection during pregnancy: a report of 5 cases from Saudi Arabia
cord-270077-mfl0iagr	2015	We used [(18)F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K(i)) in responsive lymphoid tissue. The [ 18 F]-FDG mean K i in bone marrow prior to MERS-CoV exposure was five-fold higher (0.03 ± 0.006 SD) compared to that observed in the LNs but did not follow the pattern of LN changes observed after virus challenge (Fig. 3b) . We monitored 18 F-FDG uptake primarily in lymphoid tissues at different locations in response to aerosol MERS-CoV challenge in NHPs. A group of mediastinal LNs showed a specific pattern of changes in K i up to 29 days post-virus exposure that correlates to K i changes in axillary lymph nodes. This study extends the use of kinetic modeling of [ 18 F]-FDG uptake during lung inflammation to host immune response after MERS-CoV exposure in rhesus macaques.
cord-270258-9vgpphiu	2016	To identify factors which can predict pneumonia development and progression to respiratory failure at the early course of the disease, we evaluated MERS-CoV infected patients managed in a tertiary care center during the 2015 MERS outbreak in Korea. To identify factors which can predict pneumonia development and progression to respiratory failure at the early course of the disease, we reviewed the electronic medical records of who were diagnosed with MERS-CoV infection and admitted at Samsung Medical Center, a 1950 tertiary care university hospital which managed the largest number of MERS-CoV infected patients as a single center during the 2015 Korean MERS outbreak. The present analysis of predictive factors for pneumonia development and progression to respiratory failure using variables obtained by day 3 of symptom onset could be conducted owing to the observation of entire clinical course of the disease from the exposure to MERS-CoV.
cord-270534-ebkwv4zo	2018	
cord-271004-gtmo5ixs	2017	title: Influenza is more common than Middle East Respiratory Syndrome Coronavirus (MERS-CoV) among hospitalized adult Saudi patients BACKGROUND: Since the initial description of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), we adopted a systematic process of screening patients admitted with community acquired pneumonia. An observational, laboratory-based study of outbreaks of middle East respiratory syndrome coronavirus in Jeddah and Riyadh, kingdom of Saudi Arabia Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Hospital-Associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study Middle East Respiratory Syndrome-Coronavirus (MERS-CoV): a case-controlstudy of hospitalized patients The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study
cord-271211-frkk6w0a	2020	The Chinese government has taken emergency measures to control the outbreak and has undertaken initial steps in the diagnosis and treatment of 2019 novel coronavirus infection disease (COVID‐19). A study in South Korea showed that many environmental surfaces of patients with MERS were contaminated by MERS-CoV, and virus RNA was detected from environmental surfaces within 5 days after the last positive PCR of patients'' respiratory samples. 12 Guangzhou CDC also found SARS-CoV-2 in the house of a confirmed patient, 13 which serves as evidence of contact transmission. 20 The Lancet also reminded doctors not to ignore SARS-CoV-2 transmission via ocular surfaces as infected droplets and bodily fluids may easily contaminate the human conjunctival epithelium. 27 A study showed that during the outbreak of SARS-CoV, of all exposed health care workers, 7.5% were asymptomatic SARSpositive cases. SARS-CoV-2 viral load in upper respiratory specimens of infected patients
cord-271244-6m8sbbi1	2020	They were not considered to be highly pathogenic to humans until the outbreaks of severe acute respiratory syndrome corThe coronaviruses that circulated before that time in humans mostly caused mild infections in immunocompetent people [2] . In 2018, the World Health Organization (WHO) held its annual review of the Blueprint list of priority diseases, where coronaviruses were considered and included. These diseases, given their potential to cause public health emergencies of international concern (PHEIC) and the absence of efficacious drugs and vaccines, are considered to need accelerated research and development [3] . In conclusion, it is time to translate research findings into more effective measures, as with other priority diseases [7] , such as a vaccine or effective therapeutic options, aimed at controlling viruses with clear epidemic potential, and to prioritize those interventions, to reduce and control the negative impact of diseases such as those caused by CoV, including the new emerging 2019-nCoV. Severe fever with thrombocytopenia syndrome -a bibliometric analysis of an emerging priority disease
cord-271504-t3y1w9ef	2020	
cord-271512-owidim7o	2015	The Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). We report a new case of MERS-CoV infection in a 9-month-old child complicated by severe respiratory symptoms, multi-organ dysfunction, and death. T he Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV) first reported in the Kingdom of Saudi Arabia (KSA) in September 2012. Despite all this extensive screening, and in contrast to what was observed by our colleagues dealing with adult cases in the hospital, our pediatric department could identify only one case of MERS-CoV in a 9-month-old child known to have nephrotic syndrome. Middle East respiratory syndrome coronavirus (MERS-CoV) -update Middle East respiratory syndrome coronavirus (MERS-CoV) -update Middle East respiratory syndrome coronavirus (MERS-CoV) -update Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study
cord-271648-m2c5bvuj	2020	Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. However, unlike SARS-CoV, human-to-human transmission of MERS-CoV is not easy and has not been confirmed except in cases of very close contact with infected patients in health care settings [67] . Similar to the adaptation of SARS-CoV to human host, MERSr-CoVs that are circulating in bats had to undergo several amino acid changes in RBD of S protein to become capable of infecting camels and humans ( Figure 2 ) [74] . S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS) coronavirus S protein neutralizes the virus in a rhesus macaque SARS model
cord-271681-jmoyy8rb	2016	
cord-271723-8qoozmgk	2020	
cord-272306-92rz2byz	2018	Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection Ribavirin and interferon-alpha2b as primary and preventive treatment for Middle East respiratory syndrome coronavirus: a preliminary report of two cases Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study Clinical outcomes of current medical approaches for Middle East respiratory syndrome: A systematic review and meta-analysis
cord-272622-2wceu3o9	2016	
cord-272710-uq2idlca	2016	title: Macro Domain from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Is an Efficient ADP-ribose Binding Module: CRYSTAL STRUCTURE AND BIOCHEMICAL STUDIES The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) encodes the conserved macro domain within non-structural protein 3. This study provides structural and biophysical bases to further evaluate the role of the MERS-CoV macro domain in the host response via ADP-ribose binding but also as a potential target for drug design. Variations in strength of the hydrogen bond and orientation of the side chain in Asp residues may result in differential binding affinities of ADP-ribose observed in macro domains of MERS-CoV (K d 2.95 M), SARS-CoV (K d 24 M) (36), and HCoV-229E (K d 28.9 M) (41) . Structural analysis revealed that differences in the context of hydrogen bonds formed by the conserved Asp with ADPribose and residues in ␣1 helices in macro domains of MERS-CoV, SARS-CoV, and HCoV-229E may result in differential binding affinities for ADP-ribose.
cord-272932-devmy5yx	2016	Moreover, no seroconversion was found among 53 close contacts by anti-MERS IgG antibody enzyme-linked immunosorbent assay (ELISA) of paired serum samples. To evaluate both the serological response of this MERS patient before discharge and the risk of transmission, a set of serum samples from the patient and paired serum samples collected at least 14 d apart from the close contacts of the MERS patient during his trip and hospital admission in China, were tested for MERS-CoV using an inactivated MERS-CoV-based ELISA. We used an inactivated MERS-CoV particle-based ELISA to analyze serum samples from the imported MERS-CoV patient and his close contacts for the presence of IgG against MERS-CoV. A lentivirus-based MERS-CoV pseudovirus neutralization test was performed to confirm the presence of MERS-CoV-specific antibodies in serum samples from the patient. All 53 paired serum samples from the close contacts were below the cut-off value, negative for MERS-CoV by ELISA (Figure 3 ).
cord-273182-djb0ozrt	2020	Recently, we reported cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2 and MERS-CoV with Flebogamma R DIF 5 and 10% and Gamunex R -C, two currently available intravenous IGs (IVIG) [23] . Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2 and MERS-CoV by: ELISA techniques; and well-established neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT 50 titers ranging from 4.5 to >5 (Figure 2 ). This neutralizing activity correlates with the cross-reactivity to different coronavirus antigens observed in ELISA-binding assays with IVIG, as shown in a previous study [23] . • Intravenous immunoglobulin products were tested against severe acute respiratory syndrome coronavirus 2 in cell culture neutralization assays.
cord-273391-vmtfn78x	2020	
cord-273626-zy8qjaai	2018	This illness has been named Middle East respiratory syndrome and the pathogen (MERS-CoV) has been shown to be a type of coronavirus that is highly related to SARS-CoV. Another suitable and well-established model is the common marmoset (Saguinus mystax), which can show more severe clinical signs than rhesus macaques when infected with MERS-CoV. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir Middle East Respiratory Syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques Studies of severe acute respiratory syndrome coronavirus pathology in human cases and animal models Infection, replication, and transmission of middle east respiratory syndrome Coronavirus in Alpacas
cord-273893-3nd6ptrg	2013	
cord-274007-zndtddty	2020	For Middle East respiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contact investigation; 3 patients (23%) died. Principles of management of coronavirus disease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. General principles regarding management of COVID-10 during pregnancy include early isolation, aggressive infection control procedures, testing for SARS-CoV-2 and coinfection, oxygen therapy as needed, avoidance of fluid overload, empiric antibiotics (because of secondary bacterial infection risk), fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations (Box 2).
cord-274122-n9jnu2ah	2014	Coronaviruses encode papain-like proteases (PLpro) that are often multifunctional enzymes with protease activity to process the viral replicase polyprotein and deubiquitinating (DUB)/deISGylating activity, which is hypothesized to modify the innate immune response to infection. Further, we compared the ability of MERS-CoV PLpro and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) PLpro to block innate immune signaling of proinflammatory cytokines. In this study, we demonstrate the deISGylating and deubiquitinating (DUB) activities of the papain-like protease from MERS-CoV, and provide new information on the potential role of coronavirus protease/DUBs to inhibit the innate immune response. Our results suggest that PLpro might contribute to the modulation of innate immune responses upon SARS-CoV and MERS-CoV infection, however, the exact mechanism and the role of coronavirus PLPs and their associated DUB and deISGylating activities in these processes remains to be determined.
cord-274480-aywdmj6o	2014	
cord-274506-fzcuu4ma	2019	
cord-275138-033r259v	2014	
cord-275216-dnt88ycw	2020	
cord-275313-mfyff9ne	2016	
cord-275404-hv3y4x4g	2014	
cord-276193-cngz535o	2016	
cord-276769-th7iou21	2020	Despite physical health consequences, COVID-19 pandemic has created stress and anxiety, as result there is an increased risk of mental illnesses both in the infected and normal individuals. Although bats are thought to be the source of origin for SARS-CoV-2, the intermediate animal that caused the transmission of virus to humans, is still unknown [3] . The individuals at higher risk of developing severe disease after contracting the infection should be give the priority for treatment and providing the mangeemtn and health servicesConsidering the importance of COVID-19 in the aspects of the asymptomatic spread of the virus and adverse health impacts, it is deemed necessary to investigate the factors associated with the rate of infectiousness and severity of symptoms. After originating in bats, SARS-CoV-2 emerged in Wuhan, spread all over the world through human to human transmission, and infected millions of individuals.
cord-277337-ij0dn77h	2015	
cord-277781-v9hw1cdi	2014	
cord-277823-vijh6x1l	2019	A serological survey of Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted among dromedary camels and herbivorous animals sharing the same pasturage in Ethiopia. One of camel serum that showed a high antibody titer in the neutralization test by live MERS-CoV was treated as a positive control. According to the results of the previous study, antibody titers of ≥16 are treated as positive in neutralization test using VSV-MERS/GFP. Cows that were antibody positive in the neutralization test using VSV-MERS/GFP or cELISA were different animals and both were antibody negative in the neutralization test using MERS-CoV. S1-ELISA was not sensitive compared to other tests because only 16 serum samples were positive and they required an antibody titer of ≥64 in VSV-MERS/GFP. The present study shows that the neutralization test using VSV-MERS/GFP, S1-ELISA, and cELISA are as specific to MERS-CoV infection as the serological tests, although their sensitivities slightly differ. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study
cord-278182-75u57fw1	2020	
cord-278238-w1l8h8g8	2017	Nisreen MA Okba, V Stalin Raj and Bart L Haagmans Middle East respiratory syndrome coronavirus (MERS-CoV) is a cause of severe respiratory infection in humans, specifically the elderly and people with comorbidities. The other candidate MVA-S, a viral-vector-based vaccine, induced systemic neutralizing antibodies and mucosal immunity which conferred protection against MERS-CoV challenge and reduced virus shedding in vaccinated camels [52 ] Therefore, this vaccine candidate may provide a means to prevent zoonotic transmission of the virus to the human population. Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody protects rabbits from MERS-CoV infection T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice The recombinant Nterminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection
cord-278648-hkvurb2k	2017	
cord-278839-uu2wlpmp	2020	In 2009, during the H1N1 flu pandemic, an increased ratio of female to male cases was verified, in which pregnant women developed more complications, as severe acute respiratory syndrome, and higher mortality compared to the general population (30, 31) . Additionally, infection by the Lassa virus in pregnant women shows high levels of placental replication, and the risk of maternal-fetal mortality increases with the duration of pregnancy (38, 39) . At first, contagion occurred through contact with some infected animals but, soon there were the first reports of human-to-human transmission (93), The virus was identified as belonging to the coronaviridae family and was designated SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) (94). Chen and collaborators, verified alteration in calcium and albumin levels in the blood of pregnant women with SARS-CoV-2 infection (124) , which could potentially increase the severity in COVID-19 (125) .
cord-278939-z6kiee09	2020	As previous work has highlighted the potential of traditional Chinese medicines as a source of potential novel drugs (Ling, 2020) , we have not included details on such studies investigating the antiviral activity of remedies comprising portions of numerous plant species in this review. (2020) virtually screened 83 compounds found in Chinese traditional medicines for activity against the RNA-dependent RNA polymerase of SARS-CoV-2, identifying theaflavin, an antioxidant polyphenol, as a potential inhibitor. Several authors have utilised virtual computer docking models to screen for potential compounds that could bind to and inhibit key proteins present in SARS-CoV (Liu and Zhou, 2005; Toney et al., 2004; Wang et al., 2007) , highlighting the potential antiviral activity of compounds such as sabadinine and aurantiamide acetate. Several large in vitro screening studies searching for inhibitory activity of naturally occurring compounds against SARS-CoV have been performed, mainly on Chinese medicinal herbs (Li et al., 2005; Wang et al., 2003) .
cord-279255-v861kk0i	2020	Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Recently, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID19) , emerged in late 2019, and it has posed a global health threat, causing an ongoing pandemic in many countries and territories (1) . Health workers worldwide are currently making efforts to control further disease outbreaks caused by the novel CoV (originally named 2019-nCoV), which was first identified in Wuhan City, Hubei Province, China, on 12 December 2019.
cord-279503-w4tn03w0	2019	
cord-279557-hk77e3pp	2013	
cord-279733-c0w9bw5u	2016	title: Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response. In non-specialized epithelial cells as well as a subset of specialized immune cells that are susceptible to MERS-CoV infection, 16, 18, 27 type I IFN production is an important part of the host innate immune response and is initiated by ubiquitously expressed cytoplasmic viral sensors in the retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) family in response to the detection of viral pathogen-associated molecular patterns such as double-stranded RNA (dsRNA). Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response
cord-279976-juz9jnfk	2020	METHODS: Based on recently published literatures, official documents and selected up-to-date preprint studies, we reviewed the virology and origin, epidemiology, clinical manifestations, pathology and treatment of 2019-nCoV infection, in comparison with severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV) infection. The COVID-19 generally had a high reproductive number, a long incubation period, a short serial interval and a low case fatality rate (much higher in patients with comorbidities) than SARS and MERS. Chinese Center for Disease Control and Prevention (CCDC) identified a novel beta-coronavirus called 2019-nCoV, now officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Gorbalenya et al., 2020) , that responsible for the pandemic. Further search words were above keywords, "SARS" OR "SARS-CoV" OR "severe acute respiratory syndrome", "MERS" OR "MERS-CoV" OR "middle east respiratory syndrome", in combinations of with "spike protein" OR "genome" OR "reproductive number" OR "incubation period" OR "serial interval" OR "fatality rate" OR "clinical characteristics" OR "pathology" OR "autopsy" OR "treatment".
cord-279979-3ecnbqom	2017	
cord-280029-g1k3zlax	2020	
cord-280350-ay4cnzn5	2013	
cord-280624-7v8xuicg	2020	
cord-280941-ds6x0yym	2018	
cord-281364-syg0wo77	2014	
cord-281529-2rec51xg	2013	
cord-281802-9k6klcno	2015	
cord-282279-zmfcfbo8	2018	
cord-282293-pdhjl508	2016	
cord-282554-hlcgutzf	2020	Most coronaviruses cause only mild upper respiratory infections, but sometimes they cause fatal respiratory disease and outbreaks, as experienced in cases of SARS-CoV or MERS-CoV. This disaster has been warned until recently that new mutants of coronavirus can occur anytime. As much as the 2015 MERS-CoV outbreak, we are also learning a lot of lesson from this disaster. Because epidemic is a national disaster, not only medical institutions but also governments have to be active. Our country is excellent at coping with this disaster, thanks to the experiences that we have gained during the 2015 MERS-CoV outbreak. And this outbreak is expected to have a greater amount of transmission than the 2015 MERS-CoV. Health workers, the government, and the people will need to unite to overcome this disaster. Clinical features of patients infected with 2019 novel coronavirus in Wuhan Surveillance case definitions for human infection with novel coronavirus (nCoV)
cord-282560-tofppr3b	2020	
cord-283586-o8m6xdra	2014	Abstract Serological, molecular and phylogenetic analyses of a recently imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) in Greece are reported. Although MERS-CoV remained detectable in the respiratory tract secretions of the patient until the fourth week of illness, viraemia was last detected 2 days after initiation of triple combination therapy with pegylated interferon, ribavirin and lopinavir/ritonavir, administered from Day 13 of illness. An upsurge of Middle East respiratory syndrome coronavirus (MERS-CoV) infection has been recently described in countries of the Arabian Peninsula resulting in exported cases from these countries to the European Union [1] . Published reports propose the use of known antivirals based on extrapolation of data from: (i) the severe acute respiratory syndrome (SARS) epidemic that was also associated with the circulation of a novel coronavirus; (ii) in vitro data; (iii) animal experimental infections and therapy data; and (iv) limited clinical data for actual MERS-CoV infections [2] [3] [4] .
cord-283709-y59h5bw8	2014	We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with a prototype human MERS-CoV to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. INTERPRETATION: The similarity of virus tropism and replication competence of human and dromedary MERS-CoV from the Arabian peninsula, and genetically diverse dromedary viruses from Egypt, in ex-vivo cultures of the human respiratory tract suggests that dromedary viruses from Saudi Arabia and Egypt are probably infectious to human beings. We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with the prototype human MERS-CoV EMC strain to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. To assess the infection potential of dromedary camel Middle East respiratory syndrome coronavirus (MERS-CoV) strains for humans, genetic analysis should be complemented with phenotypic characterisation in physiologically relevant invitro cell cultures.
cord-283966-eln8ljjj	2014	Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases. Animals from the Arabian Peninsula had high neutralizing serum activities overall and reciprocal antibody titers <320-1,280, which support recent infection with MERS-CoV or a highly related virus. Expanding upon these studies, we used in the present study a recombinant MERS-CoV spike protein immunofluroescence assay (rIFA) augmented by a validated protein microarray (10, 21) , followed by MERS-CoV-specific neutralization assay, to screen 651 dromedary serum samples from the United Arabian Emirates. In the tested panel of camel serum samples, vIFA titers corresponded well to titers determined by rIFA and generally equal to or higher than titers in the rIFA (Table 1) To confirm results from affinity assays with results from a functional test, we determined endpoint virus neutralization titers by using a microneutralization test against MERS-CoV and BCoV.
cord-284057-pdjz4z8z	2016	
cord-284234-9cd2v6bt	2020	
cord-284286-qfl6hehj	2016	
cord-284289-8emvca57	2018	
cord-284374-sqxlnk9e	2020	title: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries. Anesthesiologists were recommended to apply enhanced PPE (including PAPR from the middle of the outbreak) when managing all MERS-related patients because they were most directly exposed to the aerosol-producing high-risk procedures, such as endotracheal intubation and extubation. Almost all hospitals generally have positive-pressure operating rooms and they may experience an outbreak without facilities that are prepared for perioperative management of MERS patients, as our hospital did in 2015. First, although the previous guidelines recommended that asymptomatic MERS-exposed patients be managed as general patients undergoing surgery, we applied standard PPE to HCWs and we performed MERS-CoV PCR screening twice.
cord-284581-fl2nt4ak	2019	
cord-284845-on97zu6w	2016	
cord-285039-9piio754	2019	
cord-285900-3rr0j5tk	2016	To investigate why masking a negative epitope led to enhanced neutralizing immunogenicity of the MERS-CoV RBD vaccine, we performed a competition assay between neutralizing mAbs and mutant-RBD-induced mouse serum for the binding of wild type MERS-CoV RBD. Using the MERS-CoV RBD as a model, we singly mask selected epitopes using host-derived glycan probes, and then measure the corresponding changes in the vaccine''s overall neutralizing immunogenicity. To apply the NII strategy to vaccine design, we successfully enhanced the efficacy of the MERS-CoV RBD vaccine in virus challenge studies by masking its strong negative epitope (that is, the epitope containing Thr579, with an NII of À 3.0) with a glycan probe. Third, our study demonstrates that masking an immunodominant non-neutralizing epitope with a negative NII value on the surface of the MERS-CoV RBD core structure can shift host immune responses towards the neutralizing epitopes in the RBM region, providing means to overcome the limitation of viral subunit vaccines from vaccine design.
cord-286072-kgpvdb42	2020	
cord-286298-pn9nwl64	2020	Another group of researchers reported that the virus originated from bats based on the genome sequence of SARS-CoV-2, which is 96% identical to bat coronavirus RaTG13. These factors include, but are not limited to: (1) travel to or contact with individuals who have recently visited Wuhan, China, or other places experiencing an outbreak; (2) close contact with persons who are diagnosed positive for the disease, such as healthcare workers caring for patients with SARS-CoV-2; (3) contact with droplets and secretions (produced by sneezing or coughing) from an infected person and eating or handling wild animals native to China such as bats. These factors include, but are not limited to: (1) travel to or contact with individuals who have recently visited Wuhan, China, or other places experiencing an outbreak; (2) close contact with persons who are diagnosed positive for the disease, such as healthcare workers caring for patients with SARS-CoV-2; (3) contact with droplets and secretions (produced by sneezing or coughing) from an infected person and eating or handling wild animals native to China such as bats.
cord-286472-pqtem19t	2020	
cord-286631-3fmg3scx	2020	title: Comparison of confirmed COVID‐19 with SARS and MERS cases ‐ Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta‐analysis The trigger for rapid screening and treatment of COVID-19 patients is based on clinical symptoms, laboratory, and radiographic findings that are similar to SARS and MERS infections. In this study, we attempted to distinguish the clinical symptoms, laboratory findings, radiographic signs, and outcomes of confirmed COVID-19, SARS, and MERS patients. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients
cord-286683-mettlmhz	2020	
cord-286703-ipoj13va	2017	
cord-286741-h3oix9zc	2020	
cord-287156-3plpi6i9	2020	Among the seven coronaviruses that affect humans (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV, and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. 8, 9 Additionally, three HCoVs responsible for outbreaks involving high case fatality rates have been detected in humans in the last two decades: the severe acute respiratory syndrome (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV and the new coronavirus disease 2019 (COVID-19) ( Table 1) . Principal features of severe acute respiratory syndrome (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV and the most recent coronavirus disease 2019 (COVID19) . Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission
cord-287159-bjccnp7u	2017	
cord-287222-wojyisu0	2020	Of the first 99 laboratory-confirmed patients, 49 (49%) had been exposed to HSWM, which was reported to be the possible initial source of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [5] . New Coronavirus Infection Diagnosis and Treatment Scheme (Trial Version) published by Military Support Hubei Medical Team also put forward that for mild to moderate COVID-19 patients, corticosteroids should not be given principally and highdose corticosteroid pulse therapy was not recommended. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19)
cord-287527-ep6ug9c3	2018	
cord-287758-da11ypiy	2020	The increase in studies related to SARS-CoV-2 during the first semester in 2020 has allowed the rather speedy identification of promising therapeutic targets for both developing immunotherapies and producing/identifying antiviral drugs. 5, 64 So far, structural proteins and enzymes that participate actively in the process of viral replication are the most investigated targets for the development of molecules for anti-CoVs therapies (FIG. Based on results from previous studies as well, nelfinavir was considered a likely therapy for COVID-19 after its indication for clinical trials as a promising anti-SARS drug. 218 In addition to this well-known antitumor effect, imatinib has also shown in-vitro antiviral properties against several virus, such as infectious bronchitis virus (a viral model for studying the role of tyrosine kinase activity during CoV infection), by interfering with virus-cell fusion, 219 and other RNA viruses including coxsackie virus, 220 hepatitis C virus, 221 Ebola, 222 among others, mainly by blocking viral entry or egress from the host cell.
cord-287761-73qgx58i	2017	
cord-287886-41isp0wj	2016	AIM: To summarize the reported Middle East respiratory syndrome-coronavirus (MERS-CoV) cases, the associated clinical presentations and the outcomes. We also searched MEDLINE and PubMed for the keywords: Middle East respiratory syndrome-coronavirus, MERS-CoV in combination with pediatric, children, childhood, infancy and pregnancy from the initial discovery of the virus in 2012 to 2016. We searched MEDLINE and PubMed for the keywords Middle East respiratory syndrome-coronavirus, MERS-CoV, in combination with pediatric, children, childhood, infancy and pregnancy from the initial discovery of the virus in June 2012 until April 19, 2016. Middle East respiratory syndrome-coronavirus (MERS-CoV) was first isolated in 2012 from a patient in the Kingdom of Saudi Arabia (KSA). Middle East respiratory syndrome-coronavirus (MERS-CoV) was first isolated in 2012 from a patient in the Kingdom of Saudi Arabia (KSA). Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study
cord-287953-prn8cnvo	2017	However, a number of hypotheses were generated to explain the spread, including: excessive patients'' freedom in seeking medical care at only large hospitals, inadequate quarantine, questionable government transparency, such as belated reports of infected hospital names, and the cultural social norm of visiting patients as standard etiquette ( Choe, 2015a ( Choe, , 2015b ; Korea Centers for Disease Control and Prevention, 2015 ) . Using a macro-level system dynamics modeling approach, our study intends to investigate the effect of operational decisions, such as patient-room design, occupancy control at emergency room and patient-visitor management, on the patient-care performance, such as number of infected patients (secondary infections) and financial burden on patients. The model illustrated in Fig. 3 depicts a high-level overview dynamics model of causal relationships between operational decisions (patient room designs, occupancy control at emergency room, patient-visitor management) and patient care performance (number of infected patients and average cost per patient).
cord-288167-976qxja2	2018	title: Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection BACKGROUND: Information on the duration of replicative Middle East respiratory syndrome coronavirus (MERS-CoV) shedding is important for infection control. This study examined the duration for detecting MERS-CoV sub-genomic mRNA compared with genomic RNA in diverse respiratory specimens. In the present study, replicative MERS-CoV was detected in sputum or transtracheal aspirate for up to 4 weeks after symptom development in MERS-CoV-infected patients with severe pneumonia. In conclusion, replicative MERS-CoV was detected in lower respiratory tract specimens for up to 4 weeks after symptom development, which was well correlated with the detection of genomic RNA. In upper respiratory tract specimens, the detection of sub-genomic mRNA and genomic RNA did not correlate. Middle East respiratory syndrome coronavirus (MERS-CoV) genomic RNA (upE) titers in sputum and transtracheal aspirates with vs.
cord-288389-z0sz1msj	2014	title: Travel-related MERS-CoV cases: an assessment of exposures and risk factors in a group of Dutch travellers returning from the Kingdom of Saudi Arabia, May 2014 BACKGROUND: In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). METHODS: All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. Investigation of an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Middle East respiratory syndrome coronavirus (MERS-CoV) infections in two returning travellers in the Netherlands World Health Organization: Case-Control Study to Assess Potential Risk Factors Related to Human Illness Caused by Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
cord-288409-idq780jb	2016	title: Knowledge, Attitudes and Behaviours of Healthcare Workers in the Kingdom of Saudi Arabia to MERS Coronavirus and Other Emerging Infectious Diseases Objectives: The aim of this survey was to assess the knowledge, attitudes, infection control practices and educational needs of HCWs in the Kingdom of Saudi Arabia to MERS coronavirus and other emerging infectious diseases. The majority of respondents believed that patients with MERS-CoV and other emerging infectious diseases should be managed in specialised centres, but a significant proportion also agreed that general hospitals also had a role in managing such patients. A high proportion of respondents agreed that emergency department overcrowding, poor hand hygiene and mask use contributed to the risk of HCW being infected with MERS-CoV. This study also showed significant proportion with personal experience of MERS-CoV either as HCW at institutions caring for cases or being investigated for possible infection following contact with cases [10] .
cord-288589-bt9429bh	2013	However, since November 2012, Saudi Arabia has also hosted a new fatal viral infection: the Middle East respiratory syndrome coronavirus (MERS-CoV). The first known occurrence of MERS-CoV in human was reported in a patient with severe acute respiratory infection in April 2012, in Jordan. There are many reasons to convince us that MERS-CoV represents a high risk: a deadly virus that can be transmitted from person to person, a mass gathering of millions of people from different parts of the world at the epicenter of the infection, an incubation period that provides enough time for pilgrims to return home and disseminate the virus, ceremonies that place relatives and friends in close contact with infected individuals when they return, and signs and symptoms that can easily be mistaken for common postpilgrimage flu-like syndromes. Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission Middle East respiratory syndrome coronavirus (MERS-CoV), update
cord-288670-1vlowf2n	2020	
cord-288859-19jwawrm	2017	title: High reproduction number of Middle East respiratory syndrome coronavirus in nosocomial outbreaks: mathematical modelling in Saudi Arabia and South Korea Therefore, the IDEA model was used to evaluate and compare the MERS R 0 values from the outbreaks in both KSA and South Korean hospitals. Since the IDEA model is parameterized using epidemic generation time, incidence case counts were aggregated at serial intervals of six, seven and eight days in the present study [10] . The IDEA model was fitted to the daily KSA and Korea MERS-CoV case data according to the onset date. Figure 3 shows that the IDEA model provided well-fitted curves for the cumulative data regarding South Korean MERS symptom-onset dates for all cases. The present study used the IDEA model to estimate R 0 values from the MERS outbreaks in KSA and South Korea. Best-fit reproduction number (R 0 ) by serial intervals of Middle East respiratory syndrome in South Korea, 2015, using the incidence decay with exponential adjustment model.
cord-289003-vov6o1jx	2018	Abstract We present here the proceedings of the 5th seminar on emerging infectious diseases, held in Paris on March 22nd, 2016, with seven priority proposals that can be outlined as follows: encourage research on the prediction, screening and early detection of new risks of infection; develop research and surveillance concerning transmission of pathogens between animals and humans, with their reinforcement in particular in intertropical areas ("hot-spots") via public support; pursue aid development and support in these areas of prevention and training for local health personnel, and foster risk awareness in the population; ensure adapted patient care in order to promote adherence to treatment and to epidemic propagation reduction measures; develop greater awareness and better education among politicians and healthcare providers, in order to ensure more adapted response to new types of crises; modify the logic of governance, drawing from all available modes of communication and incorporating new information-sharing tools; develop economic research on the fight against emerging infectious diseases, taking into account specific driving factors in order to create a balance between preventive and curative approaches.
cord-289096-wuegn0jg	2018	Gao 1,3,4, * Infections with bat-origin coronaviruses have caused severe illness in humans by ''host jump''. The host range expansion of coronaviruses (CoVs) from wildlife to humans via genetic recombination and/or mutations on the receptor-binding domain in the spike (S) gene is well established and results in several diseases with high fatality rates, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) [ [4] . Thus, pigs are regarded as mixing vessels for IAVs. However, pigs were not known to be susceptible to bat-origin coronaviruses until recently, when two independent groups reported the detection of novel swine enteric alphacoronaviruses (SeACoVs) distinct from known swine coronaviruses (with one group successfully isolating live virus). The isolation of SeACoV from ill piglets expands our knowledge of the host range of bat-origin coronaviruses, and potentially poses a threat to public health.
cord-289311-0wgafqdz	2017	Since the first case of Middle East respiratory syndrome (MERS) was reported in Saudi Arabia in 2012, 1,826 laboratory-confirmed cases have been documented in 27 countries, and 35.5% of these patients have died from this novel virus. A triple antiviral treatment regimen comprising subcutaneous pegylated interferon alpha-2a (180 µg per week for 2 weeks), high-dose oral ribavirin [2,000 mg loading dose, followed by 1,200 mg every 8 h (q8h) for 4 days and then 600 mg q8h for 4-6 days], and oral lopinavir/ritonavir (400 mg/100 mg q12h for 10 days) was administered to all patients regardless of disease severity, which was in accordance with the interim recommendations generated during the early period of the Korean MERS epidemic. 10 GI: gastrointestinal, HFNC: high-flow nasal cannula oxygen therapy, IFN: type 1 interferon, IVIG: intravenous immunoglobulin, LR: lopinavir/ritonavir, MERS: Middle East respiratory syndrome, PSI: Pneumonia Severity Index, Rb: ribavirin, SAPS II: Simplified Acute Physiology Score II.
cord-289520-i6pv90s9	2020	RESULTS: From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. Outbreaks, especially of novel agents, create a pressing need to collect data on clinical characterization, treatment, and validation of new diagnostics to inform rapid public health response. We compared our findings to the 2018 systematic review on SARS and MERS to determine which questions have already been addressed, what information is lacking, and provide recommendations for data sharing and clinical study designs to be conducted during the current outbreak. These observational studies are practical in the fast-paced outbreak setting, as they are easier than randomised controlled The First Few X (FFX) WHO Protocol https://www.who.int/publications-detail/the-first-few-x-(ffx)-cases-and-contact-investigation-protocol-for-2019-novel-coronavirus-(2019-ncov)-infection) What are the risk factors for death or severe illness?
cord-289535-srrfr1es	2020	One concern with vaccine development for SARS-CoV-2 is that the immune response can cause disease, often in the act of clearing the infection. Preclinical animal studies have demonstrated that DNA vaccines encoding the M, N, 3a or S proteins of the SARS-CoV-1 virus could elicit immune responses [180] [181] [182] . The S protein is the target of the only SARS-CoV-1 DNA vaccine to progress to Phase I clinical trial, delivered by bio-injector, and it was safe and induced neutralizing antibody responses [183] . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial
cord-290319-decr6wrd	2015	7 The virus isolated from dromedaries has spike proteins with conserved receptor-binding domains for the human dipeptidyl peptidase-4 receptor, 8, 9 and MERS-CoV has been detected in camels that were in close contact with people with Middle East respiratory syndrome. The fi ndings from this study suggest that young men in Saudi Arabia who have contact with camels in cultural or occupational settings are becoming infected with MERS-CoV, often without being diagnosed, and might proceed to introduce the virus to the general population in which more severe illness triggers testing for the virus and disease recognition. 6 In The Lancet Infectious Diseases, Mélanie Drolet and colleagues present the fi ndings of a timely systematic review and metaanalysis assessing the population-level and herd eff ects of HPV vaccination programmes so far.
cord-290744-m0vpizuh	2016	
cord-291014-cfnoxhtd	2018	
cord-291199-nazl2e97	2018	title: Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization These findings indicate that MERS-CoV variants with reduced neutralization sensitivity were transmitted during the Korean outbreak and that the responsible mutations were compatible with robust infection of cells expressing high levels of DPP4. We demonstrate that these mutations reduce sensitivity to antibody-mediated neutralization and are compatible with robust infection of target cells expressing large amounts of the viral receptor DPP4. Incubation of control cells with MDL28170 reduced entry driven by MERS-S WT and S protein variants, and this effect was fully rescued by directed expression of TMPRSS2 (Fig. 5A ). Collectively, our findings and previous work suggest that MERS-CoV variants with at least partial resistance to antibody-mediated neutralization can retain high infectivity for cells expressing robust amounts of DPP4 and can spread between humans. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein
cord-291367-rtmsrh16	2015	
cord-291590-24psoaer	2020	In line with such a role, ExoN-knockout mutants of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) were previously found to have a crippled but viable hypermutation phenotype. Remarkably, using an identical reverse genetics approach, an extensive mutagenesis study revealed the corresponding ExoN-knockout mutants of another betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), to be non-viable. Our study thus reveals an additional function for MERS-CoV nsp14 ExoN, which apparently is critical for primary viral RNA synthesis, thus differentiating it from the proofreading activity thought to boost long-term replication fidelity in MHV and SARS-CoV. Strikingly, we now established that the equivalent knockout mutants of MERS-CoV ExoN are non-viable and completely deficient in RNA synthesis, thus revealing an additional and more critical function of ExoN in coronavirus replication.
cord-291650-1qy6y7f0	2016	title: Infection control and prevention practices implemented to reduce transmission risk of Middle East respiratory syndrome-coronavirus in a tertiary care institution in Saudi Arabia A-IC measures include administrative support with daily rounds; infection control risk assessment; timely screening, isolation, and specimen analysis; collaboration; epidemic planning; stockpiling; implementation of contingency plans; full personal protective equipment use for advanced airway management; use of a real-time electronic isolation flagging system; infection prevention and control team on-call protocols; pretransfer MERS-CoV testing; and education. Areas of deficiencies addressed at the organization level include insufficient number of staff in highrisk areas, fit testing for high-efficiency particulate respirators (especially for ED, ICU, and direct patient care providers), overcrowding in the ED, ventilation systems in the ED, extended turnaround time of MERS-CoV test results, and awareness of the importance of early identification and isolation of suspected cases.
cord-291679-jfxqipt8	2017	The aim of this study was to determine whether risk perception was associated with personal and social variables, including trust in the media, the health care field, and government. Additionally, we sought to identify the associations of risk perception and social variables with compliance with self-quarantine guidelines and overreaction during the MERS epidemic. In this study, knowledge, trust, personal characteristics, and other social determinants were considered the main factors affecting risk perception and overreaction. Therefore, this section assessed the following personal characteristics: degree of optimism about the health policies of South Korea, willingness to sacrifice for society, responsiveness to an emergency situation, and attitude toward self-quarantine and overreaction. To assess the associations of demographic factors, knowledge, trust in social organizations, intention to sacrifice, and responsiveness to emergency situations with risk perception, multiple linear regression analyses were used.
cord-291694-nokowfdi	2013	From September 2012 to July 2013, 81 laboratory-confirmed cases of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), including 45 deaths (a case fatality ratio of 55%) have been reported from eight countries. Although the WHO has not yet issued a travel health warning for any country, nor recommended conducting on-arrival screenings at ports of entry, the infectious nature of MERS-CoV means that there is a risk of contracting the disease through infected individuals who have visited the Middle East in the preceding 10 to 14 days. We recommend partnerships between public health authorities, at national and regional levels, with the labor migration industry and migrant worker networks in establishing both institutional and policy mechanisms to ensure effective preparedness and response planning in response to a potential MERS-COV threat through labor migrants from South Asia.
cord-291916-5yqc3zcx	2020	
cord-292041-a65kfw80	2020	
cord-292092-o6s5nw49	2015	title: Conservation of nucleotide sequences for molecular diagnosis of Middle East respiratory syndrome coronavirus, 2015 The present study was performed to assess the protocols used for the molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses detected between 2012 and 2015, including sequences from the large outbreak in eastern Asia in 2015. 5 The laboratory diagnosis of MERS-CoV infection is mainly performed using real-time reverse transcription PCR (RT-PCR) to detect viral RNA in specimens. This study was performed to analyze recent viral genomic nucleic acid sequences and to discuss the efficacy of the RT-PCR protocols for the molecular diagnosis of MERS-CoV infections. First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission Table 1 Conservation of the primer and probe region sequences of the WHO-recommended assays for the molecular diagnosis of MERS-CoV
cord-292709-4hn55wui	2017	
cord-292836-1o2ynvy3	2020	In this review, we discuss what is known about the virology, epidemiology, and disease associated with pediatric infection with the common community-acquired human coronaviruses, including species 229E, OC43, NL63, and HKU1, and the coronaviruses responsible for past world-wide epidemics due to severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus. By contrast SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) are highly pathogenic in humans, with high rates of severe pneumonia and fatal outcomes [21] . A large prospective surveillance study conducted in Norway from 2006 to 2015 that enrolled all hospitalized children aged ≤16 years with respiratory tract infections revealed that HCoVs OC43 and NL63 were detected most frequently and were epidemic every second winter [35] . Large surveillance studies of children and adults to evaluate the prevalence of all major respiratory viruses using multiplex PCR have been conducted in many settings, showing that HCoV infections are the fourth or sixth most common virus detected overall and across all age groups [33, 43] .
cord-293127-c27qh5y7	2020	
cord-293481-bmfj50fb	2020	Remdesivir or GS-5734 is a prodrug of a nucleoside analog with direct antiviral activity against several single-stranded RNA viruses, including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, preliminary data from a randomized placebo-controlled clinical trial showed that remdesivir reduces the time to recovery in patients with COVID-19 (5) , leading to an emergency-use authorization (EUA) by the U.S. Food and Drug Administration (FDA) only 2 days after the first press release from the National Institute of Allergy and Infectious Diseases (NIAID) (6) . There were strong arguments for the antiviral effect of remdesivir against coronaviruses emerging from multiple cell-based in vitro models, including primary human airway epithelial (HAE) cell cultures (25) , and, for MERS-CoV, from a mouse model of pulmonary infection (28) . After the outbreak of SARS-CoV-2 in January 2020, remdesivir was rapidly tested in a Vero E6 cell-based model that made use of direct viral quantification by rtPCR along with the antimalaria and immune-modulating drug chloroquine and known antivirals such as ribavirin and penciclovir.
cord-293505-1t3hg4wi	2019	Such large healthcare-associated (HCA) outbreaks have mainly been limited to the Kingdom of Saudi Arabia (KSA) and the United Arabian Emirates (UAE) until the spring 2015, when a single imported case of MERS returning from the Middle East initiated a cluster of 186 cases in the Republic of Korea (ROK) across at least 17 hospitals and much of the country 18 . We analyzed epidemiological datasets of laboratory-confirmed MERS patients and focused our study on eleven healthcare-associated outbreaks that were reported in KSA and ROK since 2015, when policies and procedures for case identification and comprehensive contact identification and follow up became systematic and were implemented by affected countries. We defined a HCA-outbreak as the occurrence of 5 or more laboratory-confirmed MERS-CoV infections with reported epidemiologic links between cases and during which the human-to-human transmission events were documented within a single healthcare facility, with no more than 14 days apart between cases symptom onset.
cord-293525-c7nwygl1	2019	
cord-293691-ewerquin	2020	RATIONALE: While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV) cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use. METHODS: Calu-3 cells and primary human alveolar epithelial cells (hAEC) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including Calcineurin, NFAT, or MAP kinases. To address the previously proposed antiviral activity of CsA in clinically relevant cells, we infected the human bronchial epithelial cell line Calu-3 and primary human alveolar epithelial cells (hAEC) with MERS-CoV and analyzed intracellular viral RNA and infectious particle release in presence of DMSO or CsA ( Figure 1 ). Our data demonstrated that silencing of IRF1 but not treatment by control siRNA lead to a significant increase in MERS-CoV released viral particles in CsA-treated cells ( Figure 6A , B).
cord-293871-hzes7mwt	2018	In this chapter, pretravel considerations for major non-vaccine-preventable infectious diseases are covered, including specific advice for dengue, chikungunya, Zika, Middle East respiratory syndrome coronavirus (MERS-CoV), and avian influenza. These include mosquito-borne infections such as dengue, chikungunya, and Zika, and regionally endemic severe respiratory infections such as Middle East respiratory syndrome (MERS) and some strains of avian influenza. These include mosquito-borne infections such as dengue, chikungunya, and Zika, and regionally endemic severe respiratory infections such as Middle East respiratory syndrome (MERS) and some strains of avian influenza. 25 Male-to-female, male-to-male, and femaleto-male transmission to unprotected sexual contacts of returning Following a short incubation period, with symptoms typically beginning 4-7 days (range 3-14 days) after exposure, dengue can present with a wide spectrum of illnesses, from asymptomatic infection to severe and fatal disease.
cord-293938-40zyv1h8	2016	The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. Given the documented history of coronaviruses overcoming the species barrier and causing severe disease in humans, it is important to investigate the zoonotic potential of close evolutionary relatives of common HCoVs in a culture model that recapitulates the aspects of the human airway, e.g. morphology and receptor distribution. The establishment of transgenic animal models for human disease is attainable when either the virus receptor has been identified, which is not the case for all HCoVs, or when viruses can be adapted to a different host.
cord-293966-5c466xvz	2019	
cord-294349-ps3qlho2	2020	
cord-294656-sx3tpe0y	2016	
cord-294800-akr4f5p8	2020	They also summarized that as viral load is quite high during the time of hospital admissions, use of potent antiviral agents at an early stage might prove Abbreviations: ACE2, angiotensin converting enzyme 2; AP, antigen presentation; APCs, antigen presentation cells; APN, aminopeptidase N, ARBs, angiotensin II receptor blockers; ARDS, acute respiratory distress syndrome; CDC, Centers for Disease Control; nCOVID-19, novel coronavirus disease 2019; CoVs, coronaviruses; DPP4, dipeptidyl peptidase 4; dsRNA, double-strand RNA; EC 50 , half maximal effective concentration; ED, emergency department; ELISA, enzymelinked immunosorbent assay; EUA, emergency use authorization; FDA, Food and Drug Administration; GGO, ground-glass opacity; HCV, hepatitis C virus; HIV, human immunodeficiency virus;, MHC, major histocompatibility complex; or HLA, human leukocyte antigen; ICU, intensive care unit; IL-6, interleukin 6; LPV/r, lopinavir/ritonavir; mAbs, monoclonal antibodies; MERS, Middle East respiratory syndrome; N7-MTase, N7-methyltransferase; NSAIDs, nonsteroidal anti-inflammatory drugs; PRRs, pattern recognition receptors; PUI, patient under investigation; RdRp, RNA-dependent RNA polymerase; RSV, respiratory syncytial virus; S protein, spike protein; SAM, S-adenosyl-methionine; SARS, severe acute respiratory syndrome; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2; TMPRSS2, transmembrane serine protease 2; WHO, World Health Organization.
cord-294831-pem059zk	2020	
cord-294854-rvrgcugn	2020	
cord-294856-eeh2a0t8	2020	
cord-294907-i836d6im	2020	
cord-294918-lm2ixz8n	2014	
cord-295375-nakxfhxk	2020	In this comparative study, we investigated the present status of conducting SRs on COVID-19, MERS, and SARS, appraised the methodological quality of these SRs using the a measurement tool to assess systematic reviews (AMSTAR 2), and performed a preliminary examination of the potential risk factors associated with the quality of SRs, with the aim of providing suggestions from the aspects of methodological quality for conducting and using SRs during the COVID-19 pandemic. AMSTAR, a measurement tool to assess systematic reviews; MA, meta-analysis quality of most SRs is unsatisfactory, and those on COVID-19 have higher risks of poor quality, despite the rapid actions taken to conduct SRs. Teams that may want to conduct a SR should focus on the study design and focus on improving the quality of the SR. Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis
cord-295433-olmein3q	2019	Initial studies investigating animal sources of the virus from "wet markets" in the Guangdong province of China suggested that Himalayan palm civets and raccoon dogs were the most likely hosts responsible for human transmission [22] ; however, the role of bats as the original animal reservoir hosts of SARS-CoV was speculated as similar viruses were detected in them [27, 28] . A recent study found that 16 out of 30 camel workers surveyed in Saudi Arabia show evidence of prior MERS-CoV infection via seroconversion and/or virus-specific CD8+ T cell responses without any history of significant respiratory disease. The primary bat species being used to study the bat immune response to virus infections in vitro and in vivo are Pteropus alecto (black flying fox), Rousettus aegyptiacus (Egyptian rousette), and Artibeus jamaicensis (Jamaican fruit bat). Multiple studies with PEDV, SARS-and MERS-CoVs have identified accessory proteins that can effectively inhibit an IFN response in mammalian cells [12] [13] [14] [91] [92] [93] [94] [95] .
cord-295559-yc8q62z8	2013	Coronavirus S proteins are Class I viral fusion proteins like the HIV envelope (env), influenza hemagglutinin (HA) and paramyxovirus fusion (F) glycoproteins [17] , which typically require protease cleavage between the S1 and S2 domains ( Figure 1A ) to permit conformational changes in S2, activated by receptor binding and/or low pH, that mediate membrane fusion leading to virus entry and syncytia formation [3, 17, 18] . In addition to entry by endocytosis, we showed that, like SARS-CoV [21, 22] , MERS pseudovirions could enter susceptible Vero E6 cells at the plasma membrane if virions were first bound to cell surface receptors at 4°C at neutral pH in the presence of NH 4 Cl to inhibit acidification of endosomes, and also treated briefly at room temperature with trypsin to cleave the viral S protein.
cord-295633-vkjcheaz	2019	
cord-295846-quhnesbr	2020	
cord-295971-jtv1jj2z	2016	BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. INTERPRETATION: Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. Excluding three patients with confi rmed MERS-CoV infection who were not identifi ed in the initial patient contact investigation (appendix p 5), the overall attack rate for patients in the emergency room was 4% (30 of 675). No MERS-CoV infection was reported in patients and visitors who had been in the emergency room on May 29 during the time period when they were exposed only to zones II (n=81) or III (n=15), while Patient 14 was confi ned to zone IV.
cord-296026-6qtip2ga	2015	
cord-296237-i9cti2ok	2020	Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. Conclusion In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. Recently, cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2, and MERS-CoV has been reported with currently available intravenous immunoglobulins (IVIG) such as Gamunex-C and Flebogamma DIF 19 . In this study, the neutralization capacity of the IVIG products Gamunex-C and Flebogamma DIF against these epidemic human coronaviruses -SARS-CoV, SARS-CoV-2, and MERS-CoV-was evaluated. Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2, and MERS-CoV by: i) ELISA techniques; and ii) well-stablished neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT50 titers ranging from 4.5 to >5 (Figure 2 ).
cord-296517-414grqif	2015	In September 2012, Middle East Respiratory Syndrome coronavirus (MERS-CoV) emerged as a novel virus that can result in severe respiratory disease with renal failure, with a case fatality rate of up to 38%. Notably, between May and July 2015, an outbreak of MERS-CoV centered in South Korea killed 36 people out of 186 confirmed cases (Promedmail.org, 2015) , with thousands quarantined as health authorities attempted to control virus spread. The 2015 MERS-CoV outbreak in South Korea began from an imported case, a 68-year-old male with a recent travel history to several Middle Eastern countries, including Bahrain, the United Arab Emirates, Saudi Arabia, and Qatar. Thus, the MERS-CoV outbreak in South Korea was driven primarily by three infected individuals, and approximately 75% of cases can be traced back to three super-spreaders who have each infected a disproportionately high number of contacts ( Figure 1A ).
cord-297062-dmiplvt2	2016	authors: Almekhlafi, Ghaleb A.; Albarrak, Mohammed M.; Mandourah, Yasser; Hassan, Sahar; Alwan, Abid; Abudayah, Abdullah; Altayyar, Sultan; Mustafa, Mohamed; Aldaghestani, Tareef; Alghamedi, Adnan; Talag, Ali; Malik, Muhammad K.; Omrani, Ali S.; Sakr, Yasser BACKGROUND: Middle East respiratory syndrome coronavirus infection is associated with high mortality rates but limited clinical data have been reported. We describe the clinical features and outcomes of patients admitted to an intensive care unit (ICU) with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: Retrospective analysis of data from all adult (>18 years old) patients admitted to our 20-bed mixed ICU with Middle East respiratory syndrome coronavirus infection between October 1, 2012 and May 31, 2014. We performed a retrospective study to describe the clinical features and outcomes of patients admitted to our ICU with laboratory-confirmed MERS-CoV infection. This report describes the clinical features and outcomes of 31critically ill patients with confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infection.
cord-297418-36j840wm	2020	However, in recent years, coronaviruses have given rise to significant diseases such as severe acute respiratory syndrome (SARS-CoV) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV) SARS-CoV infected 8,000 people, from 2002 to 2003 and had a mortality rate of approximately 10% (Marra et al., 2003) . On the other hand, evolutionary analysis based on the ORF1a / 1b, S and N genes suggests that SARS-CoV-2 is more likely to be a new coronavirus that has been introduced independently from animals to humans due to the inherent mutation property of coronaviruses in nature (Lam et al., 2020) . Severe acute respiratory syndrome (SARS) is a human disease associated with severe pneumonia and as noted above is caused by SARS-Coronavirus (SARS-CoV) (Drosten et al., 2003) . The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges
cord-297652-ut6e1ysz	2020	
cord-297691-w4cdfwv0	2020	In this special report, different strategies of using nanoparticles in dealing with coronaviruses are discussed in three parts: applications in nano-based vaccines, antiviral activity and development of diagnostic sensors. Meanwhile, as nanoparticles have been proven to have immunostimulatory effects [28] , a great deal of attention has been given to development of nano-based therapeutic agent or vaccines against different types of coronaviruses. evaluated the protective immune response stimulated by the administration of gold nanoparticles (Au NPs) conjugated with a type of coronavirus known as swine transmissible gastroenteritis virus (TGEV) in immunized mice and rabbits [29] . Recent applications of nanoparticles in developing coronaviruses sensors based on different analytical techniques and related limit of detections. The above studies on the recent applications of NPs in developing sensors based on different analytical techniques for coronaviruses and their related limit of detections are compared in Table 3 .
cord-297853-peqkcix2	2016	
cord-297954-87w2itin	2015	
cord-298350-pq1dcz3a	2016	Specific examples explored in this chapter include Nipah virus, hantavirus, West Nile fever virus, and the coronaviruses that cause severe acute respiratory syndrome and Middle East respiratory syndrome. Remarkably, researchers noted that human case patients had an association with infected animals from a concurrent and severe outbreak of respiratory disease in pigs and that there was a notable absence of illness in children. Research shows that many HPS case patients acquired the virus after having been in frequent contact with rodents or their droppings for long periods (Centers for Disease Control and Prevention, Special Pathogens Branch, 2007) . Initially, Saint Louis encephalitis virus was believed to be the cause of the human infections until WNV was isolated from the human and animal specimens. Patients infected with the SARS-coronavirus disease are likely to present to health-care facilities. Case-control study of risk factors for human infection with a new zoonotic paramyxovirus, Nipah virus, during a 1998-1999 outbreak of severe encephalitis in Malaysia
cord-298535-wmxlu3l1	2013	
cord-298773-vnmc6nqd	2015	title: Is the Debate and "Pause" on Experiments That Alter Pathogens with Pandemic Potential Influencing Future Plans of Graduate Students and Postdoctoral Fellows? This letter is about the potential impact of the debate and pause on graduate students and postdoctoral fellows and how their future plans may be affected. To gain initial insight into how the debate and research pause have affected trainees, I created an informal survey 2 days before the National Academy of Sciences meeting. These projects involve a subset of "gain of function" experiments designed to create mouse adapted viral strains, generate drug resistant viruses to understand drug mechanisms of action, understand host immunity by analyzing viruses with resistance to certain host immune pathways, and to study factors that influence transmission by the respiratory route (which was made famous by work from the Kawaoka and Fouchier labs in 2012). Third, the debate and research pause are influencing future plans of virology trainees.
cord-298941-xf2ukinp	2014	BACKGROUND: In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). Following the discovery of Middle East respiratory syndrome coronavirus (MERS-CoV) in September 2012 [2] , specimens from the 2 fatal cases in Jordan were retrospectively tested and both yielded positive results for MERS-CoV by real-time reverse transcription polymerase chain reaction (rRT-PCR), and were reported to the World Health Organization (WHO). Using newly developed serologic assays to determine MERS-CoV antibody responses among case contacts in this outbreak, epidemiologists from the JMoH, US Centers for Disease Control and Prevention (CDC), and regional partners conducted a retrospective seroepidemiologic investigation to (1) confirm whether surviving outbreak members had presence of antibodies to MERS-CoV, (2) ascertain whether viral transmission occurred among household contacts or to other healthcare personnel, and (3) describe the clinical features of all detected MERS-CoV infections in Jordan.
cord-298974-69xjc5yq	2018	The transmission connectivity networks of people infected with highly contagious Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia were assessed to identify super-spreading events among the infected patients between 2012 and 2016. e variables considered in this study were age, gender, patient type (whether the patient is a healthcare worker (HCW) or nonhealthcare worker), health outcome (dead or alive) as at the last day of follow-up, patient comorbidity status, types of exposure to known risk factors (animal contact and camel contact indirectly or directly or through consumption of camel products), and place of infection (classified as hospital, community, and household/ family). Patient 1664 was favoured (based on degree, closeness, betweenness, and eigenvector network centrality metrics) as the most important in the transmission network by having the highest number of secondary cases. In this study, several network centrality metrics (degree, betweenness, closeness, eigenvector, and 2-reach) were used to quantify the connectivity among MERS cases and to identify which patient requires prioritization for intervention.
cord-299519-hfgmmuy6	2019	A febrile acute respiratory illness with clinical, radiological, or histopathological evidence of pulmonary parenchymal disease (e.g. pneumonia or Acute Respiratory Distress Syndrome) that cannot be explained fully by any other etiology AND The person resides or traveled in the Middle East, or in countries where MERS-CoV is known to be circulating in dromedary camels or where human infections have recently occurred AND Testing for MERS-CoV is inconclusive. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: An observational study Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study Middle East respiratory syndrome coronavirus infection during pregnancy: A report of 5 cases from Saudi Arabia An observational, laboratory-based study of outbreaks of middle East respiratory syndrome coronavirus in Jeddah and Riyadh, kingdom of Saudi Arabia Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: A retrospective cohort study
cord-299608-wqa98m4v	2016	title: Building predictive models for MERS-CoV infections using data mining techniques In this paper, we apply two data mining techniques in order to better understand the stability and the possibility of recovery from MERS-CoV infections. In healthcare, data mining techniques have been widely applied in different applications including: modeling health outcomes and predicting patient outcomes, evaluation of treatment effectiveness, hospital ranking, and infection control [3] . In this paper, we build several models to predict the stability of the case and the possibility of recovery from MERS-CoV infection. The classification models were built using a dataset of 699 records and 9 attributes and the best accuracy was achieved using decision trees induction algorithms. A new attribute was created to indicate the record type, such that the dataset can be used to predict the recovery from MERS-CoV. A new attribute was created to indicate the record type, such that the dataset can be used to predict the recovery from MERS-CoV.
cord-299621-m4kdkmey	2017	Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified from a 60-year-old Saudi male patient admitted to a private hospital in Jeddah, Saudi Arabia on June13, 2012, with history of fever, cough, expectoration, and shortness of breath who eventually expired 11 days after admission from progressive respiratory failure. In April 2012, a cluster of cases of pneumonia occurred in health care workers of an intensive care unit in a hospital in Zarqa, Jordan, of which 2 patients died, both of whom were confirmed to be infected with the novel coronavirus by retrospective analysis of stored sample. New respiratory illness room with portable High efficiency particulate arrestors (HEPA) was created to isolate suspected MERS-CoV infected patients within the Emergency Medical Services. Until date (July 2017), there are no healthcare associated MERS-CoV Infection among patients, visitors and HCWs of our hospital and improved compliance with the IPC policies and procedures were achieved.
cord-299720-f0ny4ur5	2017	title: Risk Factors for Transmission of Middle East Respiratory Syndrome Coronavirus Infection During the 2015 Outbreak in South Korea Transmission heterogeneity was observed during the 2015 Korean outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Transmission heterogeneity was a significant characteristic of the 2015 South Korean outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection [1] . Epidemiological reports from the outbreak were evaluated to collect data regarding basic demographic characteristics, medical history, MERS-CoV exposure, symptoms and their onset date(s), sampling date(s), contact history, and post-exposure infection control. In the univariate analyses, transmission was associated with underlying respiratory disease, Ct value, interval from symptom onset to diagnosis, number of contacts, and pre-isolation hospitalization or ER visits. It appears that both host infectivity and the number of contacts influenced MERS-CoV transmission, whereas super-spreading events were mostly associated with a greater likelihood of encountering other people under diverse environmental conditions.
cord-299986-wuaxatrb	2020	To critically evaluate the existing options, an attempt has been made to list the drugs considered potentially useful in corona virus infections including the previous outbreaks of SARS and MERS and are tabulated ( Table 1) to derive lessons from the existing scientific literature. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays Middle Eastern respiratory syndrome corona virus (MERS CoV): case reports from a tertiary care hospital in Saudi Arabia Ribavirin and interferon therapy for critically Ill patients with Middle East respiratory syndrome: a multicenter observational study Corticosteroid therapy for critically Ill patients with Middle East respiratory syndrome
cord-300078-svu06v9c	2020	To compare the scientometric aspects of the studies on SARS, MERS and Covid-19, three separate datasets of publications on these three topics were retrieved from Scopus through three separate search strategies. Figures A1 and A2 in the Appendix illustrate the map associated with the SARS literature overlaid respectively with the average year of publication and average number of citations associated with the studies where these keywords have occurred. Maps of term occurrences based on the analysis of the title and abstract of studies on SARS, MERS and Covid-19 have also been presented in Figures 7, 8 and 9 respectively. An inspection of the maps overlaid with the average year of publications for SARS and MERS in Figures A1 and A3 in the Appendix suggests that, on average, this cohort of studies are generally the last to emerge in the published domain compared to the two other major clusters, but they receive relatively high citations on average (according to Figures A2, A4 and A6).
cord-300950-ag0sql4i	2020	Several case reports including the first report of SARS outbreak described the use of the anti-viral drug ribavirin and a corticosteroid in patients with contradictory clinical outcomes. In several studies, lopinavir/ritonavir was shown to have anti-CoV effects in vitro, in MERS-infected primate models, and in SARS-infected humans. Furthermore, in a single MERS patient, a triple-combination therapy of ribavirin, IFN and lopinavir/ ritonavir resolved viremia in 2 days following initiation of treatment. [7] [8] [9] In two reports from China and Korea, the use of lopinavir/ritonavir in patients with COVID-19 improved recovery and reduced viral load. [7, 8] However, Chen et al [9] showed that lopinavir/ ritonavir and the anti-influenza treatment Arbidol had no clinically significant improvement in 134 people with mild COVID-19. [17] In an effort to combat inflammation and improve clinical outcome, corticosteroid use has been described in SARS, MERS, and COVID-19.
cord-301016-9t7v7ipt	2015	We determined that different residues at position 1020 establish distinct interand intra-helical interactions and affect the stability of the six-helix bundle formed by the HRs. A similar effect on stability was observed for a nearby mutation (T1015N) that increases MERS-CoV infection efficiency in vitro. Data herein indicate that the heptad repeat region was a major target of adaptive evolution in MERS-CoV-related viruses; these results are relevant for the design of fusion inhibitor peptides with antiviral function. Motivated by the notion that evolutionary analyses can provide information on the molecular events that underlie host shifts and, more generally, host-pathogen interactions 19 , we investigated the evolutionary history of S proteins in MERS-CoV and related betaCoVs. Specifically, we aimed to determine whether natural selection drove the evolution of specific regions and sites that may contribute to variation in host range or replication efficiency.
cord-301103-idu4j78a	2019	The nucleotide and amino acid sequences of MERS-CoV Spike protein gene were used to analyze the recombination, genetic diversity and phylogenetic relationship with selected sequences from Saudi Arabia. Recently, in another study, total 530 nucleotides deletion was observed in Spike gene from serum samples collected from Taif, Saudi Arabia and a novel genetic variant of MERS-CoV was designated as a quasispecies [29] . Multiple substitutions of amino acids were observed in RBD, part of Spike gene from a bat sample collected from Uganda and the recombination in the S1 subunit of the Spike gene was observed and it was expected that this variation likely to play an important role in the emergence of MERS-CoV causing disease in human [30] . The detection of MERS-CoV in human and camel determining the genetic diversity among Spike gene will further help researchers as well as health authority to design and develop an effective disease management and control strategies in the Kingdom of Saudi Arabia.
cord-301313-9595vm0k	2020	Here, we describe development of serological assays for the detection of virus neutralizing antibodies and antibodies to the nucleocapsid (N) protein and various spike (S) domains including the S1 subunit, and receptor binding domain (RBD) of SARS-CoV-2 in ELISA format. Using a wellcharacterized cohort of serum samples from PCR-confirmed SARS-CoV-2 and patients PCR-confirmed to be infected with seasonal coronaviruses and other respiratory pathogens, we validated and tested various antigens in different platforms developed in-house as well as a commercial platform. We evaluated SARS-CoV-2 specific antibody responses in severe and mild cases using serum samples collected at different times post-disease onset from three French PCR-confirmed CoVID-19 patients. We tested sera for SARS-CoV-2 specific antibodies using different ELISAs. Following infections, all three patients seroconverted between days 13 and 21 post onset of disease (Figure 1) , and antibodies were elicited against the SARS-CoV-2 S and S1 subunit including the N-terminal (S1 A ) domain and the receptor binding domain (RBD).
cord-301547-d4wt9dqp	2020	
cord-301633-t8s4s0wo	2020	Similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infections, patients exhibited symptoms of viral pneumonia including fever, difficulty breathing, and bilateral lung infiltration in the most severe cases [1] . A range of disease has been observed highlighted by fever, dry cough, shortness of breath, and leukopenia; patients have included mild cases needing supportive care to severe cases requiring extracorporeal membrane oxygenation; however, compared to SARS-CoV (10% mortality) and MERS-CoV (35% mortality), the 2019-nCoV appears to be less virulent at this point with the exception of the elderly and those with underlying health conditions. In the early part of the outbreak, the absence of infection in health care workers argued for inefficient human to human spread and distinguished 2019-nCoV from both SARS-CoV and MERS-CoV.
cord-301730-flv5lnv8	2020	Despite the previous positive reports of plant-based medications, no successful clinical trials of phyto-anti-COVID drugs could be conducted to date. Medicinal plant extracts have been reported to impede the replication of several viruses including human immunodeficiency virus (HIV), hepatitis B virus (HBV), poxvirus, severe acute respiratory syndrome (SARS) virus, and herpes simplex virus type 2 (HSV-2) (Vermani and Garg, 2002; Kotwal et al., 2005; Huang et al., 2006) . Different researchers are investigating diverse plant forms based on ethnopharmacological data to find effective anti-CoV drugs with novel action mechanisms especially targeting viral replication. Moreover, creating an effective phyto-anti-COVID drug during this pandemic may provide an idea on the duration and the strategy required for the development of potent plant-based therapeutics in case of such random viral outbreaks (Figure 1) .
cord-302983-3v5bc80z	2020	title: Health literacy in the general population in the context of epidemic or pandemic coronavirus outbreak situations: Rapid scoping review OBJECTIVE: The aim of this rapid scoping review, for which only studies from the general population were considered, was to describe the extent of existing research on HL in the context of previous coronavirus outbreaks (SARS-CoV-1, MERS-CoV and SARS-CoV-2). METHODS: We searched major databases and included publications of quantitative and qualitative studies in English and German on any type of research on the functional, critical and communicative domains of HL conducted in the context of the three outbreaks in the general population. Therefore, the aim of this rapid scoping review, for which only studies from the general population were considered, was to describe the extent of existing research on HL in the context of previous coronavirus outbreaks (SARS-CoV-1, MERS-CoV and SARS-CoV-2).
cord-303272-1w8epdht	2013	title: Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. We tested the sera for the presence of IgG antibodies reactive with MERS-CoV, SARS-CoV, and human coronavirus OC43 S1 antigens in a protein microarray. plaque reduction neutralisation tests for bovine coronavirus and MERS-CoV (B): two representative sera are shown (numbers 15 and 5, corresponding to camel ID numbers in table 2) in dilutions of 1/40, 1/160, and 1/640 as well as the virus input control. Sera were tested for IgG antibodies reactive with MERS-CoV, SARS-CoV, and human coronavirus OC43 S1 antigens in a protein microarray (fi gure 1).
cord-303289-qoukiqr7	2017	We carried out RT‐PCR on 306 nasal and 315 rectal swabs and tested 243 sera for antibodies to detect coronavirus infections in apparently healthy horses in Saudi Arabia and Oman. RNA extracts were tested for evidence of conserved coronavirus nucleic acid genetic sequences using previously reported RT-PCR assays (Chu et al., 2014) , RTqPCR assay for MERS-CoV upE gene (Corman et al., 2012) , RTqPCR assay for ECoV (Miszczak et al., 2014) , and a RTqPCR assay for HKU23 reported below. T A B L E 5 Cross-neutralization titres (denoted as reciprocal titres) for Middle East respiratory coronavirus (MERS-CoV), bovine coronavirus (BCoV) and equine coronavirus (ECoV) in hyperimmune or naturally infected sera known to be positive for different coronaviruses NR460pig antiserum to porcine respiratory coronavirus 1,200 a <20 <20 <20 <20 Similarly, a BCoV immune serum from an experimentally infected gnotobiotic calf showed detectable, but 16-fold reduced antibody titre with ECoV but no cross-reaction with MERS-CoV.
cord-303670-fma8wq4z	2017	
cord-303786-snch80z7	2018	
cord-303915-14yfs4pa	2013	
cord-303917-2tu707ng	2020	
cord-303941-3lg1bzsi	2015	Although bats are not in close contact with humans, spillover of viruses from bats to intermediate animal hosts, such as horses, pigs, civets, or non-human primates, is thought to be the most likely mode to cause human infection. Currently, bats have been considered to be natural reservoirs of SARS-CoV, MERS-CoV, NiV, HeV, Ebola virus, and Marburg viruses. The viruses discussed above tend to be restricted to certain geographic regions with a particular bat reservoir, such as HeV and NiV associated with flying foxes in Australia and Southeast Asia and Ebola virus associated with Egyptian fruit bats in Africa. Bats have been proposed as the natural reservoirs of viruses causing severe diseases in humans, such as NiV and HeV in Southeast Asia and Australia, Ebola and Marburg viruses in Africa, SARS-CoV in Asia and MERS-CoV in Middle East.
cord-304030-6ve5plea	2018	title: Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10 In order to determine if the nucleocapsid protein of MERS-CoV (MERS-N) plays a role in viral–host interactions, a murine monoclonal antibody was generated so as to allow detection of the protein in infected cells as well as in overexpression system. The A549 transduced cells expressed relatively high MERS-N protein on both day 2 and 10 post-selection in an antibiotics medium as shown in Figure 2A . Fold regulations of antiviral response genes by MERS-N protein was compared with negative control cells, which were expressing LacZ, by using the 2 − C T method. Out of the nine host genes identified using stably transduced A549 cells, proinflammatory cytokine/chemokines TNF, IL6, IL8, and CXCL10 were reported to be up-regulated in MERS-CoV infected cells [3, 17, 20] . CXCL10 regulation has been reported in MERS patients [18, 19] as well as MERS-CoV infected cells [3, 17, 20] .
cord-304054-sn7rswab	2020	Abstract Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (CoV), first identified in Saudi Arabia in 2012. Although the natural reservoir of MERS-CoV infection and mode of transmission to humans is not known, one factor appears to be common to all primary cases; they are epidemiologically linked to the Middle East region. Cross-sectional surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels and other mammals in Egypt Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Middle East respiratory syndrome coronavirus infection during pregnancy: a report of 5 cases from Saudi Arabia Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission Transmission of Middle East Respiratory syndrome coronavirus infections in healthcare settings
cord-304057-d2r92nji	2018	title: Sero‐prevalence of Middle East respiratory syndrome coronavirus (MERS‐CoV) specific antibodies in dromedary camels in Tabuk, Saudi Arabia A primary sero‐prevalence study of MERS‐CoV preexisting neutralizing antibodies in Dromedary camel serum was conducted in Tabuk, western north region of KSA, in order to assess the seopositivity of these animals and to explain their possible role in the transmission of the infection to Human. 11, 16, 17 Results have shown that a high number (85%) of dromedary camels from the different farms of Tabuk Riyadh and screened by ELISA test showed that 74% of the animals were found to have antibodies to MERS-CoV. 7 In the same study, 264 archived serum samples collected from dromedary camels from 1992 to 2010 in Riyadh and Kharj were also analyzed by ELISA and showed a high seroprevalence (92%) of MERS-CoV neutralizing antibodies. Middle East respiratory syndrome coronavirus neutralizing serum antibodies in dromedary camels: a comparative serological study Seroprevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) specific antibodies in dromedary camels in
cord-304227-rbr2un1u	2013	title: Updated Information on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Guidance for the Public, Clinicians, and Public Health Authorities, 2012–2013 This report summarizes epidemiologic information and provides updates to CDC guidance about patient evaluation, case definitions, travel, and infection control as of September 20, 2013. This report summarizes epidemiologic information and provides updates to CDC guidance about patient evaluation, case definitions, travel, and infection control as of September 20, 2013. Health-care providers in the United States should continue to evaluate patients for MERS-CoV infection if they develop fever and pneumonia or acute respiratory distress syndrome (ARDS) within 14 days after traveling from countries in or near the Arabian Peninsula. CDC continues to recommend that clusters ¶ of patients with severe acute respiratory illness (e.g., fever and pneumonia requiring hospitalization) be evaluated for common respiratory pathogens and reported to local and state public health departments. More detailed MERS-CoV-related interim guidance about patient evaluation, case definitions, travel, and infection control is available at http://www.cdc.gov/coronavirus/mers/index.
cord-304271-vyayyk50	2020	
cord-304943-thg4fqi2	2020	SARS-CoV-1 disease was originated in Guangzhou city of China and the start of 2020 was again a challenging year for this country because of extremely contagion 2019-novel coronavirus (2019-nCoV) disease outbreak. Chinese health ministry took immediate action to investigate and control the disease, including quarantine measures, continuous observation of contacts, clinical and epidemiological data collection from infected people and development of diagnostic tools and efficient treatment protocols. 9 Previous study revealed that wet markets of southern China including Wuhan and Guangzhou cities have the greater risk of spreading novel corona viruses, because of wild animal trading and the absence of biosecurity measures. In-vitro studies indicated that Remdesivir has been successful in the termination of viral RNA replication, 30, 32 and showed effectiveness against the MERS-CoV, SARS-CoV and other bat originated coronaviruses. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
cord-305134-s7h6bpof	2020	It is likely that multiple systems contribute to thrombosis in COVID-19 patients, such as activation of coagulation, platelet activation, hypofibrinolysis, endothelial cell dysfunction, inflammation, neutrophil extracellular traps, and complement. 60, 82 Taken together, these results indicate that most COVID-19 patients have an activated coagulation system that is associated with increased levels of d-dimer; however, it is unlike classic DIC since there is little change in PT and the thrombocytopenia is generally mild. [95] [96] [97] [98] [99] There is clear evidence for activation of different cell types, such as lung epithelial cells, macrophages, neutrophils, endothelial cells, and platelets, as well as different systems, such as coagulation, inflammation, and complement, in the lungs of COVID-19 patients (Figure) . We found that plasma levels of extracellular vesicle TF activity were increased in severe influenza virus patients and were associated with mortality. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infects lung epithelial cells and endothelial cells (ECs), which leads to the recruitment of a variety of immune cells, such as macrophages and neutrophils.
cord-305175-1wg0wodr	2020	Studies of its immunogenicity have shown that vaccination of animals (mice and primates) induces a robust humoral immune response that lasts for at least six months. A study of the vaccine protectivity conducted in a model of transgenic mice carrying the human DPP4 receptor gene showed that our vaccination protected 100% of the animals from the lethal infection caused by the MERS-CoV virus (MERS-CoV EMC/2012, 100LD(50) per mouse). For this Studies of the immunogenicity of the combined vector vaccine revealed the induction of long-term humoral immunity in mice, while the mean titer of glycoprotein-specific antibodies equaled 1 : 121,775 two weeks after vaccination at a dose of 10 7 v.p. per mouse. [13] , immunization of transgenic mice carrying the human DPP4 receptor gene with a ChAdOx1 MERS vaccine at a dose 10 8 v.p. per mouse was shown to protect 100% of the animals from a lethal infection with MERS-CoV.
cord-305317-08a1oin2	2014	Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus of the Coronaviridae family that causes a severe respiratory disease with a high case fatality rate. 2, 3, 6, 8, 22, 24 During the largest so farepublished outbreak of MERS-CoV that occurred in Al-Hasa, Saudi Arabia, in 2013, 4 health care facilities were affected through transfer of patients but also possibly because of repeated introductions of cases from the community. Studies about the effectiveness of infection control measures will provide answers and eventually promote safety in health care facilities both for patients and HCWs. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Investigation of an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Interim infection prevention and control recommendations for hospitalized patients with Middle East respiratory syndrome coronavirus (MERS-CoV)
cord-305422-t8azymo7	2020	The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. The virus is highly homologous to the coronavirus (CoV) that caused an outbreak of severe acute respiratory syndrome (SARS) in 2003; thus, it was named SARS-CoV-2 by the World Health Organization (WHO) on February 11, 2020, and the associated disease was named CoV Disease-19 (COVID-19) [1] . Whenever possible, we will try to compare COVID-19 with SARS and another CoV-caused disease, Middle East respiratory syndrome (MERS, an outbreak in 2012). Due to the lack of experience with the novel CoV, physicians can mainly provide supportive care to COVID-19 patients, while attempting a variety of therapies that have been used or proposed before for the treatment of other CoVs such as SARS-CoV and MERS-CoV and other viral diseases ( Table 2) .
cord-305534-936peb1n	2020	The severe acute respiratory syndrome coronavirus−2 (SARS-CoV-2) has been recently identified as the culprit of the highly infectious, outbreak named coronavirus disease 2019 (COVID-19) in China. While it is known that COVID-19 manifests similarly to the 2003 Severe Acute Respiratory Syndrome (SARS) and the 2012 Middle East Respiratory Syndrome (MERS), primarily affecting the pulmonary system, the impact of the disease extends far beyond the respiratory system and affects other organs of the body. In the severe disease state, the patient''s clinical course is complicated by the development of pneumonia with ARDS, acute hypoxic respiratory failure, and/or death (7) . Several retrospective studies have consistently reported pulmonary manifestations in patients with COVID-19, which include cough, shortness of breath, sputum production, respiratory failure, and ARDS (Table 1) (5, 7, (9) (10) (11) (12) (13) (14) (15) (16) (17) . Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study
cord-305582-3hmsknon	2020	
cord-305745-9lngdjow	2020	Chalcones isolated from Angelica keiskei were shown to inhibit both SARS-CoV proteases PLpro and 3CLpro in enzymatic, FRET-based (Table 2) and molecular docking studies (Park et al. As Table 2 demonstrates, the compounds showed generally higher inhibitory potential against SARS-CoV PLpro than when tested against the other viral proteases using fluorogenic methods, which is likely related to genomic variations in the single amino acid sequences. In particular, herbacetin, quercetin and isobavachalcone (Fig. 3) were identified as promising antiviral leads against SARS-and MERS-CoV based on their broad-spectrum activity against the viral proteases 3CL and PL of both CoVs, the number of relevant literature data, and the availability of the compounds from different plant sources. However, despite some promising inhibitory activities of flavonoids against SARS-and MERS-CoV in vitro, none of these compounds have been tested in vivo using animal and/or human cell models.
cord-305773-ikm1famj	2015	Based on the first case of Middle East respiratory syndrome found in China, a clinical research in combination with radiological findings was studied. Differential imaging diagnosis on the basis of epidemiological and experimental pathogen detection is helpful for clinical diagnosis of MERS, even in distinguishing from SARS and pneumonia caused by H7N9 avian influenza. Middle East respiratory syndrome (MERS), also known as camel flu, is a viral respiratory illness caused by a novel human beta-coronavirus (CoV) [1e3] . On the sixth day after his hospitalization, MERS-COV was negative via the virological detection of sputum, and his body temperature had decreased to be normal, which indicated that the virus has a direct relationship with the fever. 1) Small pieces of high density shadows in the two lower lungs near the heart edge were observed during the early period via chest X-ray examination, suggesting that it firstly progressed to pneumonia (about one week). Middle East respiratory syndrome coronavirus (MERS-CoV) infection: chest CT findings
cord-305871-w1quh4fx	2017	Furthermore, inoculation of inactivated plasma on Vero E6 cells did not result in any cytopathic effect (CPE) even after 7 days of incubation and three consecutive passages, nor the detection of MERS RNA compared to pretreatment samples which showed complete CPE within 2 to 3 days postinoculation and log viral RNA titer ranging from 9.48 to 10.22 copies/ mL in all three passages. Furthermore, inoculation of inactivated plasma on Vero E6 cells did not result in any cytopathic effect (CPE) even after 7 days of incubation and three consecutive passages, nor the detection of MERS RNA compared to pretreatment samples which showed complete CPE within 2 to 3 days postinoculation and log viral RNA titer ranging from 9.48 to 10.22 copies/ mL in all three passages. Similar to SARS-CoV, there is no proven evidence so far of transfusion-transmitted MERS-CoV infections, 25 but the presence of viral RNA in plasma and serum of acute patients raises this concern especially in endemic areas like Saudi Arabia.
cord-306004-amv0los1	2019	Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. MERS-CoV infection in these animals merely causes mild upper respiratory tract infection [17, 18] , but seroepidemiological studies showed that this virus has been circulating in dromedary camels for decades, suggesting the efficient transmission of MERS-CoV in this species [19] [20] [21] [22] . Given the fact that experimental in vivo infection studies and DPP4 expression analysis in different animal species revealed that dromedary camels are not the only animals in which MERS-CoV has an upper respiratory tract tropism [17, 18, 83, 84] , it is then relevant to question whether other animals can potentially spread MERS-CoV as well.
cord-306923-eujbxdqi	2018	Data on the time intervals between a patient''s presentation or admission to a healthcare facility and the first specimen sample have been limited in patients suspected and screened for MERS-CoV by a real-time reverse-transcription polymerase chain reaction (rRT-PCR) test, as it might correlate with recovery delay intervals. This chart review study was based on information from multicenters and a large sample size, and it provides valuable information on factors associated with prolonged or shorter recovery delay of patients suspected and screened for MERS-CoV by the rRT-PCR test. The study evidence supports that longer recovery delay was seen in patients with older age, MERS-CoV infection, ICU admission, and abnormal radiology findings in a sample of patients diagnosed by rRT-PCR. Factors associated with recovery delay in a sample of patients diagnosed by MERS-CoV rRT-PCR: A Saudi Arabian multicenter retrospective study
cord-307067-cpc1yefj	2020	For Middle East respiratory syndrome coronavirus (MERS-CoV), we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with ChAdOx1 MERS. A prime-boost regimen of ChAdOx1 MERS boosted antibody titers, and viral replication was completely absent from the respiratory tract tissue of these rhesus macaques. Viral load was higher for lower respiratory tract tissue obtained from animals vaccinated with ChAdOx1 GFP (n = 6) than from animals receiving a prime-only (n = 6) or a prime-boost regimen of ChAdOx1 MERS (n = 2) (Fig. 4B ). Notably, antigenic differences have been reported between S proteins from the Middle East and Africa (8), potentially affecting the efficacy of a vaccine based In conclusion, we show that a single vaccination with ChAdOx1 MERS results in protection against disease progression and virus replication associated with MERS-CoV challenge in the rhesus macaque, and a prime-boost regimen reduced viral replication further.
cord-307109-nz8qvuw6	2020	The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. To predict new zoonotic coronavirus jumps across species and to understand the rate of virus spread among people, it is crucial to determine whether SARS-CoV-2 is mutating to improve its binding to human receptors for infection. Clinical observations in animals and humans showed that MERS-CoV infections were mediated by both virus replication and host inflammatory responses. However, therapeutic treatment with human monoclonal antibodies did not protect against the severe disease or the loss of lung function induced by MERS-CoV in animal models (20) .
cord-307405-qk1ruj5q	2014	To investigate potential transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) to health care workers in a hospital, we serologically tested hospital contacts of the index case-patient in Saudi Arabia, 4 months after his death. To investigate potential transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) to health care workers in a hospital, we serologically tested hospital contacts of the index case-patient in Saudi Arabia, 4 months after his death. Hospital infection control staff administered a brief, standardized questionnaire to both groups of HCWs. Information was collected on HCW demographics, job duties, and symptoms of respiratory disease during June 15-July 4, 2012, which corresponds to the period when the case-patient was hospitalized and an incubation period of 2-10 days, based on MERS-CoV natural history information available at the time of investigation. In October 2013 (4 months after the case-patient''s death), a blood specimen (<20 mL) was collected from each HCW and transported first to the Ministry of Health Western Regional Laboratory in Saudi Arabia and then to the US Centers for Disease Control and Prevention for MERS-CoV testing.
cord-307811-6e3j0pn7	2020	Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. Previous studies of many other viruses suggested that SARS-CoV-2 S protein may use other molecules on host cell surface as attachment factors to facilitate binding to the high-affinity receptor ACE2. 36 A recent study suggested that HS may bind to the receptor binding domain (RBD, the C-terminal region of the S1 subunit, Fig. 2 ) of the SARS-CoV-2 spike protein and change its conformation. 38 In this study, we systematically examined and compared the binding of the SARS-CoV-2 S protein subunits, full-length molecule and its trimer to different HS using microarray experiments (Fig. 2) . In addition to binding protein-based receptors, many viruses can interact with cell surface glycans, including GAGs and sialic acid-containing oligosaccharides.
cord-307853-m1q1sjr4	2020	title: Exploring the intrinsic dynamics of SARS-CoV-2, SARS-CoV and MERS-CoV spike glycoprotein through normal mode analysis using anisotropic network model In this study we have examined the intrinsic dynamics of the prefusion, lying state of trimeric S protein of these viruses through Normal Mode Analysis using Anisotropic Network Model. MERS-CoV spike shows unique dynamical motion compared to the other two S protein indicated by low RMSIP, spectral overlap and cosine correlation value. A detailed study to explore the intrinsic dynamical motion of the prefusion lying state spike protein trimer is needed for proper understanding of its function from conformation perspective. RMSIP computes quantitative comparison value between the sets of normal modes and expressed as: Structural alignments of the models were done using PyMol. We have computed the eigenvalues of first hundred non-zero normal modes of the SARS-CoV-2, SARS-CoV, and MERS-CoV spike (S) proteins in the lying state ( Fig. 1 ).
cord-307995-8q7efrqk	2016	Middle East respiratory syndrome coronavirus (MERS-CoV): summary and risk assessment of current situation in the Republic of Korea and China -as of 19 Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study A family cluster of Middle East Respiratory syndrome coronavirus infections related to a likely unrecognized asymptomatic or mild case Community case clusters of Middle East respiratory syndrome coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: a descriptive genomic study Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study KSA MERS-CoV Investigation Team.Hospital outbreak of Middle East respiratory syndrome coronavirus Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study
cord-308061-hz7fsn2g	2013	Data of a preliminary infection study in lung explants indeed indicate that MERS-CoV reaches higher replication levels and shows broader cell tropism in the lower human respiratory tract than does SARS-CoV. This rate is better than that noted in patients with SARS: only a third of laboratoryconfi rmed cases yielded virus in upper-respiratory-tract samples. 5 The values reported by Assiri and colleagues also show that viral loads in the upper respiratory tract are higher than in patients with MERS who were treated overseas and, thus, who were investigated later in the disease course. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission
cord-308340-p2iqzyv4	2013	
cord-309010-tmfm5u5h	2017	Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. Transnasal infection with MERS-CoV following adenoviral transduction of human DPP4 yielded an expansive, (Fig 7A) interstitial pneumonia with severe alveolar epithelial cell necrosis and infiltration of mainly macrophages, lymphocytes, and fewer neutrophils (Fig 7B) . Different mouse models of acute pneumonia differ widely, with an obvious strong dependence on pathogen-specific features of virulence and spread, route of infection, infectious dose and other factors.
cord-309081-v098m4dc	2017	
cord-309089-ex9nh1yi	2020	Since the first reports on COVID-19 disease, it appeared clear that Acute respiratory distress syndrome (ARDS) accounted for a significant number of deaths among infected patients and that ARDS should be regarded as the hallmark immune-mediated clinical consequence in SARS-CoV-2, similarly to what described for SARS-CoV and MERS-CoV infections [11] . As shown by previous data in the literature, increased circulating levels of pro-inflammatory cytokines (eg, Interferon γ, interleukin (IL-) 1B, IL-6, IL-12) and chemokines (CXCL10, and CCL2) are associated with pulmonary inflammation and extensive lung involvement in SARS patients, similarly to what happens in MERS-CoV infection [13] . In mice infected with SARS-CoV, the clinical features of the syndrome showed an age-dependent increase in severity (similarly to what observed in humans), which was related to an increased level of pro-inflammatory cytokines and chemokines, paralleled by a reduction in T-cell responses [78] .
cord-309239-6lso1w0o	2016	The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen first described from Saudi Arabia in 2012 [1] that can cause severe respiratory disease and death in roughly 36% of infected humans [2] . There is considerable field and experimental evidence that dromedary camels serve as an important reservoir host involved in transmission to humans [3] [4] [5] [6] [7] [8] , but whether other livestock such as goats, sheep, and horses play a role in transmission has only been assessed indirectly. The objective of this study was to determine if goats, sheep, and horses can be infected with MERS-CoV and assess their potential importance in viral transmission. Sheep, goat kids and horses were each inoculated intranasally with 1.4 × 10 6 to 1.9 × 10 6 plaque-forming units (PFU) of a low passage human isolate of MERS-CoV (strain HCoV-EMC/2012) propagated in Vero E6 cells as described previously [11] .
cord-309518-seonrtn3	2019	BACKGROUND: Noninvasive ventilation (NIV) has been used in patients with the Middle East respiratory syndrome (MERS) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied. [9] [10] [11] [12] While NIV may initially avoid the need for intubation and invasive mechanical ventilation (MV) , several studies have reported high failure rates and the need for invasive ventilation among patients with severe acute respiratory distress syndrome (ARDS) and an association with increased mortality. 12 In a recent analysis from the LUNG SAFE study on unselected patients with ARDS, NIV was associated with higher intensive care unit (ICU) mortality in patients with the ratio of partial pressure of oxygen to the fraction of inspired oxygen (PaO 2 /FiO 2 ) lower than 150 mm Hg. 12 The role of NIV in AHRF secondary to viral respiratory infections is unclear.
cord-309621-6jj19xpr	2017	The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. Although there have been several studies in animal models on the pathogenic mechanisms of MERS-CoV infection, little is known about the comparative pathology and inflammatory cell response in rhesus macaques or common marmosets infected with this virus. Pathological findings in the rhesus macaque tissues HE stained tissues from rhesus macaques experimentally infected with MERS-CoV demonstrate that MERS-CoV induces lesions that are primarily observed in the lungs, with varying degrees of inflammation, interstitial pneumonia (Fig 1A) , pulmonary oedema (Fig 1B) , haemorrhaging, degeneration and necrosis of pneumocytes and bronchial epithelial cells (Fig 1C) , and the infiltration of inflammatory cells. Using immunohistochemical techniques and an ISH analysis, we confirmed that MERS-CoV protein and viral RNA were distributed in the lungs of rhesus macaques and common marmosets and that they were primarily located in the pneumocytes and inflammatory cells.
cord-309734-m8miwtha	2017	Dromedary camels are the main reservoir of Middle East respiratory syndrome coronavirus (MERS‐CoV), but other livestock species (i.e., alpacas, llamas, and pigs) are also susceptible to infection with MERS‐CoV. Virus was present in nasal swabs of infected animals, and limited amounts of viral RNA, but no infectious virus were detected in the direct contact pigs. However, other animal species such as non-human primates (rhesus macaques and common marmosets), members of the family Camelidae (alpacas and llamas), rabbits and pigs have been demonstrated to be susceptible to MERS-CoV infection (Crameri et al., 2016; Falzarano et al., 2014; Haagmans et al., 2015; Vergara-Alert, van den Brand, et al., 2017; de Wit et al., 2013 de Wit et al., , 2017 . To study whether MERS-CoV might be transmitted between pigs, an experimental transmission study in this animal model was designed and performed under direct and indirect contact settings.
cord-309898-sju15hev	2020	The key result of our work is that both, the overall flexibility of upward RBD and the mobility ratio of RBDs in different conformations, represent two significant factors that show a positive scaling with virus lethality and an inverse correlation with the infection rate. Figure 2 depicts data that shows that the lowest-frequency normal modes of MERS-CoV, SARS-CoV and SARS-CoV-2 spike proteins are all associated with a swing motion of upward receptor-binding domain (RBD) to different extents. Figure 4 provides a correlation diagram for MERS-CoV, SARS-CoV and SARS-CoV-2 spike protein, where the overall flexibility of upward RBD is evaluated by the average fluctuation of open-state RBD and the mobility ratio is quantified as the ratio of maximum fluctuations over upward and downward RBDs. The data shows that both factors have positive correlation with case fatality rate and inverse relationship with the virus infectivity.
cord-310071-d195rumq	2016	The purpose of RRT were to consult the Government controlling MERS-CoV outbreak, and visit hospitals that were exposed to MERS-CoV infected patients and to advise them with an infection control strategy and rehabilitation program that would prevent the exposure of the disease in hospitals. As considering KCDC''s faults, we began to isolate close contacts early about hospitals where there were MERS patients. Through confirming with hospital officials, we conducted a consultation rapidly about closing the hospitals, isolation of patients and medical staffs and infection control in hospital. Therefore, they needed to be sent to the infection control practitioners early, so various hospital staffs were isolated who had close contact with the patients. Because isolating the room was not enough, patients on the 6th and 7th floor (not close contact MERS patient) were transferred to Daejeon Army Hospital. On the June 19th, the 170th patient was confirmed who was transferred to D hospital, had close contact with the 76th patient in the same ward.
cord-310297-sbxlz04w	2019	title: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Oman: Current Situation and Going Forward M iddle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic viral respiratory illness caused by a novel betacoronavirus, which was first reported in Saudi Arabia in 2012. 5 As of January 2019, a total of 2298 laboratoryconfirmed human cases of MERS-CoV from 27 countries have been reported, including 811 associated deaths giving a fatality rate of 35.2%. 9, 10 Between 27 January and 12 February 2019, a total of 13 additional human cases of laboratoryconfirmed MERS-CoV using real-time polymerase chain reaction (RT-PCR) were reported in Oman. Surveillance for human infection with Middle East respiratory syndrome coronavirus (MERS-CoV), WHO Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels Risk factors for primary Middle East respiratory syndrome coronavirus infection in camel workers in Qatar during 2013-2014: a case-control study Middle East respiratory syndrome coronavirus transmission among health care workers: Implication for infection control
cord-311176-dlwph5za	2018	The objective of this study is to compare the outcomes of MERS-CoV patients before and after the availability of extracorporeal membrane oxygenation (ECMO) as a rescue therapy in severely hypoxemic patients who failed conventional strategies. METHODS: We collected data retrospectively on MERS-CoV patients with refractory respiratory failure from April 2014 to December 2015 in 5 intensive care units (ICUs) in Saudi Arabia. In this retrospective cohort study, we found that ECMO rescue therapy was associated with lower in-hospital mortality, better oxygenation, and fewer organ failures compared to historical control (usual care) in patients with severe MERS-CoV. described the use of ECMO in two patients with acute respiratory failure secondary to MERS-CoV infection in France, where both patients developed severe hypoxia and increasing oxygen requirements, leading to mechanical ventilation and ECMO use. Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study
cord-311937-6hadssmh	2016	title: Middle East respiratory syndrome coronavirus in Al-Madinah City, Saudi Arabia: Demographic, clinical and survival data METHODS: A retrospective study was conducted of all confirmed MERS-CoV infections from March 2014 to May 2014 at two tertiary care hospitals in Al-Madinah region (Saudi Arabia). Epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) was expanded after exploring the large hospital outbreak in Al-Hasa, Saudi Arabia [2] . We obtained data about demographic characteristics, clinical presentation, laboratory results, diagnosis, incubation period, smoking history, comorbidities, and history of contact with camels or MERS-CoV positive patients in regions within the Madinah area. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection
cord-312038-g76cpjp7	2020	Utilizing repurposed NIC, and with the goal of developing a therapeutically effective, rapidly scalable and globally distributable antiviral therapy to reduce the spread of SARS-CoV-2, we describe an inhalable NIC formulation that can be administered using three major models or respiratory tract delivery systems: DPI, nasal spray and nebulizer. At the highest dose tested (0.125 µg/mL NIC), Vero cells with an established MERS-CoV infection exhibited an 82.2% ± 0.8% decrease in viral load compared to untreated controls after 24-hours of exposure to NIC-hLYS particles ( Fig 1D) . While brain viral titres did not exhibit further reduction from levels noted in the preliminary efficacy study, the inoculation of Vero E6 cells with viral particles obtained from lung and brain homogenates of surviving animals resulted in no observation of CPE at any of the inoculum concentrations tested, which indicates that remaining viral particles were not active.
cord-312178-tojgojjf	2020	Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or MERS, but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. The rapid spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to a pandemic of Coronavirus Disease 2019 (COVID-19) across the globe. The novel SARS-CoV-2 virus spreads rapidly, with 2-3 people infected from every index case, a reproduction number (R 0 ) or transmission rate of 2.24 -3.58 (2) . The aim of this review is to summarize what is currently known about the impact of prior coronaviruses and the novel SARS-CoV-2 infection on reproduction and pregnancy. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection during pregnancy: Report of two cases & review of the literature An Analysis of 38 Pregnant Women with COVID-19, Their Newborn Infants, and Maternal-Fetal Transmission of SARS-CoV-2: Maternal Coronavirus Infections and Pregnancy Outcomes
cord-312434-yx24golq	2020	Here, we apply bibliometric analysis along with visualization tools to analyze 15,207 publications related to human coronavirus from the Scopus database, using indicators on publication and citation, journal, country or territory, affiliation and international cooperation, author, and keyword co-occurrence cluster. Therefore, in order to accurately, effectively and systematically reveal connections within the human coronavirus field, our study applied bibliometrics and visualization methods to analyze human coronaviruses-related publications and citations, countries and affiliations, as well as journal performance, author impact and keyword cooccurrence cluster. According to these keywords, human coronavirus diseases like "SARS, " "MERS" and COVID-19 may have something worthwhile for comparison with other "infectious diseases" like "influenza" in their epidemiological characteristics; "healthcare workers, " "transmission, " "surveillance, " "quarantine, " or "isolation" may be the focuses of these studies, which can help to promote current disease control and prevention measures.
cord-312533-4u3bmb0e	2017	Recently, a great deal of evidence has suggested that a transmembrane protease, serine 2 (TMPRSS2), a type II transmembrane serine protease (TTSP), plays a critical role in SARS and Abbreviations: ARE, androgen receptor element; AEBSF, 4-(2-Aminomethyl) benzenesulfonyl fluoride hydrochloride; BHH, Bromhexine hydrochloride; CoV, coronavirus; DESC1, serine protease DESC1; EST, (2S,3S)-trans-Epoxysuccinyl-Lleucylamido-3-methylbutane ethyl ester; FDA, Food and Drug Administration; HAT, human airway trypsin-like protease; HAI-2, hepatocyte growth factor activator inhibitor 2; HGF, hepatocyte growth factor; IFITM, Interferon-induced transmembrane protein; MMP-2, matrix metalloproteinase-2; MSPL, transmembrane protease, serine 13; PAI-1, plasminogen activator inhibitor 1; PAR-2, protease activated receptor 2; PPMO, peptide-conjugated phosphorodiamidate morpholino oligomer; RBS, receptor binding subdomain; THE, human tracheal epithelial; TMPRSS2, transmembrane protease, serine 2; TMPRSS4, transmembrane protease serine 4; TTSP, type II transmembrane serine protease; vRNPs, viral ribonucleoproteins. Although FDA-approved inhibitors that specifically inhibit TMPRSS2 are not yet available, some drugs such as camostat and nafamostat that have inhibitory activity against a variety of serine proteases have been approved for the treatment of other diseases and also suppress influenza virus and coronavirus infections.
cord-312670-hi3fjne4	2019	Zusätzlich zu diesen ständig im Menschen zirkulierenden Varianten wurden in den vergangenen Jahren zwei CoV im Menschen gefunden, nämlich SARS-CoV und MERS-CoV, die aus dem Tierreservoir auf den Menschen übergegangen sind und bei einem deutlich größeren Anteil der Infizierten schwere virale Pneumonien mit tödlichem Verlauf auslösen [25, 28] . Obwohl die Mehrzahl der Infektionen mit den vier endemischen CoV nur leichte Atemwegserkrankungen verursacht, können alle HCoV auch schwere Hier steht eine Anzeige. Inwiefern diese sekundären Infektionen auf die intensivmedizinische Behandlung und Beatmung zurückzuführen sind oder ein spezifisches grundsätzliches Risiko einer CoV-Infektion darstellen, ist noch nicht verstanden. Jedoch ist eine spezifische Labordiagnostik bei Verdacht auf eine Infektion mit endemi-schen CoV bei harmlosem Verlauf und Patienten ohne besonderes Risiko für die Entstehung von Komplikationen auch nicht indiziert. Bei der typischerweise unspezifischen Klinik von MERS-CoV-Infektionen sollte auch die Möglichkeit einer Infektion mit anderen Pathogenen in Betracht gezogen werden [26] . RKI (2015) Schwere respiratorische Erkrankungen in Verbindung mit Middle East Respiratory Syndrome Coronavirus (MERS-CoV).
cord-312691-ynh84b98	2016	title: Predictors of MERS-CoV infection: A large case control study of patients presenting with ILI at a MERS-CoV referral hospital in Saudi Arabia BACKGROUND: A case control study to better characterize the clinical features, laboratory, and radiological abnormalities associated with MERS-CoV infection in order to help with early identification of this syndrome from other respiratory infections. METHODS: Eighty patients admitted to a hospital in Riyadh, diagnosed with MERS-CoV infection based on RT-PCR were matched on age, sex, and the presence of a co-morbid condition on a basis of 1:2 to other patients admitted with respiratory symptoms and tested negative for MERS-CoV on RT-PCR. First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission Laboratory-confirmed case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Malaysia: preparedness and response Middle East Respiratory Syndrome Coronavirus: a case-control study of hospitalized patients
cord-312692-jv3425w1	2019	Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). To assess innate immune responses in the lungs of Tg2, non-Tg, and C57BL/6 mice, all animals received intranasal administration of PBS with or without (B) Immunohistochemical analysis of hDPP4 expression in human, Tg2, and non-Tg mouse tissues stained with an anti-hDPP4 polyclonal antibody. Tg2 mice aged 10 and 25 weeks showed increased expression of cytokines and chemokines associated with migration of T cells and activation of macrophages, including IP-10, IL-6, IL-13, MCP-1, IFN-␥, MIP-1␣, MIG, and IL-12, in the lungs at day 5 and/or 7 p.i. This result is the same as that observed in a hDPP4 knock-in mouse model reported by Coleman et al.
cord-312740-2ro2p77q	2020	A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARSor MERS-CoV proliferation in animal models which is significantly different compared to that in humans. With Having a considerable number of people worldwide infected with COVID-19, scientists have identified a number of cases of broad-spectrum antiviral agents (BSAAs) that could serve as potential candidates for the treatment of the viral diseases (Andersen et al., 2020; Ianevski et al., 2018) . Corona virus SARS-CoV-2 disease COVID-19: Infection, prevention and clinical advances of the prospective chemical drug therapeutics
cord-312741-0au4nctt	2020	160, 161 Once the PAMPs from invaded viruses are detected, RIG-I and MDA5 interact with the mitochondrial antiviral signaling protein (MAVs) that is a mitochondrial membrane-bound F I G U R E 2 Escape mechanisms of innate immune response of SARS-CoV and MERS-CoV adaptor molecule, followed by the activation of several kinase complexes and multiple subsequent transcription factors (IRF3, IRF7, and NF-κB). Antiviral peptides analogous derived from these regions exhibited inhibition to the spike protein-mediated cell-cell fusion and viral entry in viruses such as SARS-CoV, MERS-CoV, as well as HCoV-229E. Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein
cord-313028-0nhgxoim	2020	
cord-313054-w90eitw9	2019	RESULTS: A total of 229 MERS-CoV cases, including 70 deaths (30.5%), were recorded in the disease outbreak news on world health organization website over the study period. Middle East respiratory syndrome coronavirus (MERS-CoV) infection is considered to cause a new viral epidemic [1] , and was first reported in a patient who died from a severe respiratory illness in a hospital in Jeddah, Saudi Arabia, in June 2012 [2, 3] . The occurrence of a large number of MERS-CoV cases and their associated deaths in the world indicate that this disease must be considered as a severe threat to public health [13] because millions of pilgrims from 184 countries converge in Saudi Arabia each year to perform Hajj and Umrah ceremony. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study
cord-313517-5ipj2z86	2019	Though the gold standard for diagnosing MERS-CoV infection in humans is still nucleic acid amplification test (NAAT) of the up-E region, an antigen capture enzyme-linked immunosorbent assay (ELISA) could also be of use for early diagnosis in less developed locations. In the present method, a step-by-step guide to perform a MERS-CoV nucleocapsid protein (NP) capture ELISA using two NP-specific monoclonal antibodies is provided for readers to develop their in-house workflow or diagnostic kit for clinical use and for mass-screening project of animals (e.g., dromedaries and bats) to better understand the spread and evolution of the virus. Nucleic acid amplification test (NAAT, e.g., real-time reverse transcription quantitative polymerase chain reaction [real-time RT-qPCR]), virus isolation, transmission electron microscopy, immunohistochemistry, and serological methods (e.g., antigen capture enzyme-linked immunosorbent assay [ELISA] and immunofluorescence assay [IFA] ) have been developed and used for MERS-CoV diagnosis [2] [3] [4] [5] [6] [7] .
cord-313684-61hkogdh	2020	Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the Wuhan City of China in December 2019 and evolved into a global pandemic. These include antivirals (remdesivir, lopinavir/ritonavir, umifenovir, and favipiravir), interferon, antimalarials (chloroquine/hydroxychloroquine), antiparasitic drugs (ivermectin and nitazoxanide), biologics (monoclonal antibodies and interleukin receptor antagonist), cellular therapies (mesenchymal stem cells and natural killer cells), convalescent plasma, and cytokine adsorber. Though several observational studies have claimed many of these agents to be effective based on their in vitro activities and extrapolated evidence from SARS and Middle East respiratory syndrome (MERS) epidemics, the currently available data remains inconclusive because of ill-defined patient selection criteria, small sample size, lack of concurrent controls, and use of intermediary outcomes instead of patient-relevant outcomes.
cord-313737-cob5hf5q	2015	1 The conference opened with Professor Tawfik Khoja outlining the challenges to infection prevention and control in the Middle East. Among the challenges he covered were public reporting and external scrutiny, hand hygiene, antibiotic resistance, the healthcare environment, surveillance and outbreaks, an increasingly elderly population, new threats [such as Ebola and Middle East respiratory syndrome coronavirus (MERS-CoV)], meticillinresistant Staphylococcus aureus (MRSA), C. Dr Phin highlighted a useful CDC toolkit providing advice on respiratory protection for healthcare workers, and also a recent BMJ review concluding that facemasks may help to prevent the spread of respiratory viruses in the community. As to which interventions we should use for each organism, this depends on organism and setting, although screening, isolation, stewardship, hand hygiene, and cleaning/ disinfection are the pillars of infection control. Dr Muhammad Halwani then gave an overview of infection control in the Middle East, focusing on acinetobacter and pseudomonas.
cord-314357-u1m7yr8f	2018	title: Evaluation of preparedness of healthcare student volunteers against Middle East respiratory syndrome coronavirus (MERS-CoV) in Makkah, Saudi Arabia: a cross-sectional study AIM: To assess the knowledge and attitude of senior medical, dental, nursing and pharmacy students toward Middle East respiratory syndrome-corona virus (MERS-CoV) in Saudi Arabia. An ANOVA test was used to determine the association of study discipline and academic year with the student knowledge score on MERS. Since its first detection in Saudi Arabia in 2012, Middle East respiratory syndrome-corona virus (MERS-CoV) has become a major health problem (Bermingham et al. This study therefore aims to assess the knowledge and attitude of senior medical, dental, nursing and pharmacy students toward MERS in Makkah, Saudi Arabia. Section 2 comprised nine items and was designed to evaluate students'' in-depth knowledge about MERS including causes, sources of transmission, mortality, clinical manifestations, prevention strategies and risk groups for MERS.
cord-314651-e4uaw5fy	2015	
cord-314867-qg3hl5ft	2019	Bavachin and bavachinin showed good anti-MERS-CoV activities of 2.9 and 7.9 μM respectively by phenotypic cellular screening with vero cell. Total 12 compounds of bavachinin derivatives in four core structures were evaluated to figure out their anti-MERS-CoV activity and cell-cytotoxicity by cellular phenotypic screening method as shown in Table 1 . The further alkylations of phenolic OH of 1a with isopropyl and benzyl group decreased the anti-MERS activities (Entry 3 and 4 in Table 1 ). Interestingly, O-isopropyl Note and O-benzyl derivatives (2c and 2d, respectively) showed similar activity with 2a (non-substituted) better than 2b (Omethylated), but the cytotoxicity for vero cell also increased. As a conclusion, a series of 2-phenylchroman-4-one derivatives were synthesized for the chemical modifications of bavachin, and they exhibited anti-MERS activities in vero cell. We expect the study on bavachin derivatives can contribute to the development of anti-MERS drug.
cord-315234-pqn7qhm8	2015	
cord-315316-w7cn9iqp	2017	Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. TTSP family members, most notably the transmembrane protease serine type 2 (TMPRSS2), can cleave CoV fusion glycoproteins (termed spike [S] proteins), into unlocked, fusion-catalyzing forms [8, 9, 11] at the cell surface and facilitate a rapid, "early" entry. Even antibodies binding to CD81 suppressed MERS S-mediated entry [14] , indicating that several tetraspanins, including those that are not required per se for clustering hDPP4 and TMPRSS2, organize into cell-surface "webs" [15] and enclose the CoV entry factors.
cord-315437-h6xjudm0	2018	
cord-315909-vwugf0wp	2019	Here, we describe methods for in vitro serial passaging of Middle East respiratory syndrome coronavirus (MERS-CoV) to select for mutations which increase replication on semi-permissive cell lines as described in Letko et al., Cell Rep 24, 1730–1737, 2018. Forced adaptation experiments have been used to determine viral mutations that facilitate escape from drugs [4] [5] [6] , monoclonal antibodies [7, 8] , host restriction factors [9] [10] [11] , and species variation in host receptors [12] [13] [14] and to elucidate various viral mechanisms of infection and replication [15] [16] [17] . Below is the method employed to adapt MERS-CoV to a semi-permissive host receptor, Desmodus rotundus DPP4. To increase selective pressures on a viral population which is beginning to show signs of adaptation, one can apply a population bottleneck in the subsequent passage by reducing the amount of viral Evolution of MERS-CoV supernatant passaged to the next cell culture.
cord-316013-7dckgg6b	2019	
cord-317061-0bx704ao	2015	The nsp5 of the newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as 3CLpro and its canonical cleavage sites (between nsps) were predicted based on sequence alignment, but the cleavability of these cleavage sites remains to be experimentally confirmed and putative non-canonical cleavage sites (inside one nsp) within the pp1a/1ab awaits further analysis. Some cleavage sites have been identified and confirmed by previous studies, including three cleavage sites of PLpros of human coronavirus 229E (HCoV 229E), mouse hepatitis virus (MHV), SARS-CoV, MERS-CoV and infectious bronchitis virus (IBV), whose cleavages release the first 3 non-structural proteins (Bonilla et al., 1995; Kilianski et al., 2013; Lim and Liu, 1998; Ziebuhr et al., 2007) . In order to set up a more moderate and balanced criteria for protease cleavage site identification, we compared six scanning conditions with different stringency to systematically predict the 3CLpro cleavage sites on pp1a/1ab of five coronaviruses including MERS-CoV. To rapidly evaluate the proteolysis activity of MERS-CoV 3CLpro toward the predicted cleavage sites of different substrates, a sensitive luciferase-based biosensor assay was adopted.
cord-317232-qk72i0gv	2015	
cord-317389-trvleobp	2019	
cord-317403-1wrsuoy7	2015	In May 2015, Middle East respiratory syndrome coronavirus infection was laboratory confirmed in South Korea. For the index patient, MERS-CoV RNA was detectable in sputum, throat swab, and serum samples but not in a urine sample collected 9 days after symptom onset ( Table 1) . Because, to our knowledge, cases of MERS-CoV infection in South Korea have not been reported, we had to establish laboratory testing protocols to overcome vulnerabilities in the absence of appropriate epidemiologic support (i.e., generate positive controls to check for contamination and repeat testing). Although the source of infection for the index patient is unclear, phylogenetic analysis of the whole viral genome showed that the isolate from South Korea was closely related to the MERS-CoV strains isolated in Saudi Arabia in 2015. Probable transmission chains of Middle East respiratory syndrome coronavirus and the multiple generations of secondary infection in South Korea
cord-317435-4yuw7jo3	2020	Using network proximity analyses of drug targets and HCoV–host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. The high druggability of HCoV-host interactome motivates us to develop a drug repurposing strategy by specifically targeting cellular proteins associated with HCoVs for potential treatment of 2019-nCoV/SARS-CoV-2. These network proximity analyses offer putative repurposable candidates for potential prevention and treatment of HCoVs. To further validate the 135 repurposable drugs against HCoVs, we first performed gene set enrichment analysis (GSEA) using transcriptome data of MERS-CoV and SARS-CoV infected host cells (see Methods).
cord-317647-vcktnsv8	2020	
cord-317688-mr851682	2018	Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in September 2012 [1] . The first patient (index case) with MERS-CoV infection was a 68-year-old Korean man returning from the Middle East. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea Clinical implications of 5 cases of Middle East respiratory syndrome coronavirus infection in a South Korean outbreak Renal complications and their prognosis in Korean patients with Middle East respiratory syndrome-coronavirus from the central MERS-CoV designated hospital Successful treatment of suspected organizing pneumonia in a patient with Middle East respiratory syndrome coronavirus infection: a case report
cord-318181-xxc7vdnt	2018	
cord-318315-r6wqywwe	2014	We aimed to screen Hajj pilgrims admitted to healthcare facilities in 2013 with severe community-acquired pneumonia (CAP) for MERS-CoV and to determine other etiologies. METHODS: Sputum samples were collected from all pilgrims admitted to 15 healthcare facilities in the cities of Makkah and Medina, Saudi Arabia, who were diagnosed with severe CAP on admission, presenting with bilateral pneumonia. 7, 10 In recent years, the Middle East respiratory syndrome coronavirus (MERS-CoV) has also emerged as a cause of serious illness including severe pneumonia. Respiratory tract infections are common illnesses during the Hajj, 15 and pneumonia is the leading cause of hospital admission, including admission to the ICU, during the pilgrimage. 16 In the current study, as part of the Saudi MoH MERS-CoV surveillance, we investigated the etiology of severe CAP in pilgrims attending the 2013 Hajj requiring hospitalization. 7,10 Studies performed during previous Hajj seasons have reported the organism as a cause of respiratory tract infections including penumonia.
cord-318448-3bkp1mtj	2015	
cord-318585-cp76qr9f	2016	
cord-318872-0e5zjaz1	2018	
cord-318935-xsfolppr	2018	
cord-318954-pj5lsvsa	2015	
cord-319006-6f2sl0bp	2017	title: Imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection from Oman to Thailand, June 2015 Thailand reported the first Middle East respiratory syndrome (MERS) case on 18 June 2015 (day 4) in an Omani patient with heart condition who was diagnosed with pneumonia on hospital admission on 15 June 2015 (day 1). From 2012 to 21 July 2017, there have been 2,040 reported laboratory-confirmed cases and 712 deaths from Middle East respiratory syndrome coronavirus (MERS-CoV) infection in 27 countries [1] . A single imported case of Middle East respiratory syndrome (MERS) in South Korea, identified on 20 May 2015, resulted in 150 laboratory-confirmed cases, amplified by infection in hospitals and the transfer of patients within and between hospitals, and caused 15 deaths within 26 days, mainly among patients, visitors and healthcare personnel [2] .
cord-319447-xanewi59	2020	
cord-319501-a2x1hvkk	2016	Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. This suggests SARS-CoV N may interfere with RNA recognition by host immune sensors such as RIG-I and MDA5 thus achieving suppressive role in IFN production. Our group demonstrated that MERS-CoV ORF4a interacts with PACT, a cellular dsRNA-binding protein that optimally activates RIG-Iand MDA5-induced type I IFN production, in an RNAdependent manner (Siu et al., 2014c) . Infection with SARS-CoV and MERS-CoV has been accompanied with suppression of innate immune response, most notably with the suppression of type I IFN production and signaling pathways. Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses pact-induced activation of RIG-I and MDA5 in the innate antiviral response
cord-319689-33h22ikl	2018	
cord-319707-j8y9gt2o	2020	The novel coronavirus, SARS-CoV-2, is likewise a causative pathogen for severe viral pneumonia with the risk of progression to respiratory failure and systemic manifestations. Articles related to the topic were identified by following terms: "Severe Acute Respiratory Syndrome", "Middle East Respiratory Syndrome", Coronavirus disease 2019", "Neurology", "MERS", "SARS", "COVID-19", "Stroke", "Epilepsy", "Guillain-Barré Syndrome", "Encephalitis", "Myelitis", "Meningitis", "Neurological Sequels", "Polyneuropathy" and "Carotid Dissection". Several recent articles report associated cases of encephalitis, acute flaccid paralysis and other neurological symptoms, such as Guillain-Barré syndrome or ADEM, as possible complications of a HCoV infection [6] . Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome Neurological complications of middle east respiratory syndrome coronavirus: a report of two cases and review of the literature
cord-319780-rfj9t99r	2020	Analysis of the co-crystal structure suggested that the SARS spike protein binds to the active site of angiotensin converting enzyme 2 (ACE2, Li et al., 2005) . A truncated version of human recombinant ACE2, lacking the transmembrane domain, mitigated against SARS-CoV infection of cells (Li et al., 2003) and has been used in animal models to reduce symptoms of severe acute lung failure , diabetic nephropathy (Oudit et al., 2010) and cardiac hypertrophy and fibrosis . A recent cryo-EM structure suggested that ACE2 and B 0 AT1/SLC6A19 form a heterodimer which pairs up through interfaces between the two ACE2 partners (Figure 1) , with the RBD of SARS-CoV-2 spike protein binding to the peptidase active site of ACE2 suggesting that B 0 AT1/SLC6A19 may facilitate entry of the novel coronavirus. Tumor necrosis factor- convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)
cord-319784-lpmsalux	2015	title: Pilot use of a novel smartphone application to track traveller health behaviour and collect infectious disease data during a mass gathering: Hajj pilgrimage 2014 Pilot use of a novel smartphone application to track traveller health behaviour and collect infectious disease data during a mass gathering: Hajj pilgrimage 2014 1 Therefore, we conducted a pilot study using a smartphone app to examine its feasibility to track not only Hajj pilgrim KAP regarding preventive measures, but also symptom onset and participation in high-risk activities before, during, and after Hajj 2014. The first screen (first phase) is the pre-Hajj questionnaire, including data on participant demographics, pre-existing chronic diseases, vaccinations received before travel, factors influencing vaccination decision and uptake, perception of the risk of respiratory infection during Hajj, willingness to participate in highrisk activities, such as drinking unpasteurised milk, and awareness of official health recommendations provided by Saudi Arabian authorities.
cord-319877-izn315hb	2016	Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. The downregulation of ACE2 results in the excessive production of angiotensin II by the related enzyme ACE, and it has been suggested that the stimulation of type 1a angiotensin II receptor and Middle East respiratory syndrome coronavirus (MERS-CoV) encode two large polyproteins, pp1a and pp1ab, which are proteolytically cleaved into 16 non-structural proteins (nsps), including papain-like protease (PLpro), 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), helicase (Hel) and exonuclease (ExoN). Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have developed mechanisms to interfere with these signalling pathways, as shown; these subversion strategies involve both structural proteins (membrane (M) and nucleocapsid (N)) and non-structural proteins (nsp1, nsp3b, nsp4a, nsp4b, nsp5, nsp6 and papain-like protease (PLpro); indicated in the figure by just their nsp numbers and letters).
cord-320238-qbjrlog1	2020	Using an immune-focusing approach, we created self-assembling particles multivalently displaying critical regions of the MERS-CoV spike protein ─fusion peptide, heptad repeat 2, and receptor binding domain (RBD) ─ and tested their immunogenicity and protective capacity in rabbits. The use of self-assembling multimeric protein scaffold particles (MPSP) to present antigens in a multivalent virus-mimicking manner (size, repetitiveness, and geometry), has been shown to enhance vaccine-induced immune responses [7] [8] [9] [10] [11] , and to offer advantages over other multimeric antigen presentation platforms (reviewed in [12] ). We sought to design antigens capable of inducing strong immune responses against critical parts of the viral entry and fusion machinery within the MERS-CoV spike protein through immune focusing and multivalent presentation on self-assembling particles (Figure 1 ). Following the prime, RBD-LS vaccination induced antibody responses of high avidity and MERS-CoV neutralizing capacity.
cord-320548-oigyut2k	2014	
cord-320663-xypg6evo	2020	A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. Natural Killer (NK) cells are a key component of the innate immune system and are critical in the response to many viral infections in humans and animal models (1) (2) (3) . Altogether these studies show that during acute CoV infection, inflammatory monocyte-macrophages and neutrophils accumulate in the lungs and produce cytokines and chemokines that induce the activation and migration of lymphocytes, including NK cells, to the lungs, where they could be one of the main producers of IFN-γ (148). Studies have reported that patients infected with SARS-CoV-2 have lower levels of circulating NK cells and these express a greater level of inhibitory receptors (e.g., NKG2A) while producing less IFN-γ (127, 129, 130) .
cord-320709-2pnqpljt	2016	
cord-320746-iuzfexig	2015	Although much recent focus has been on the recognition of Ebola virus disease among travelers from West Africa, cases of Middle East respiratory syndrome coronavirus (MERS-CoV), including travel-associated cases, continue to be reported. Although much recent focus has been appropriately placed on the recognition of Ebola virus disease in travelers returning from West Africa, the recent increase in cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection (including travelassociated cases) is also of concern [1, 2] . Update on the epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, and guidance for the public, clinicians, and public health authorities First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities
cord-320909-p93gxjm2	2020	
cord-320921-eumuid3r	2019	Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission. Besides dromedary camels, other animal species, i.e. llamas, alpacas, and pigs have been shown to be susceptible and develop upper respiratory tract infection upon experimental intranasal MERS-CoV inoculation [9] [10] [11] . We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ). We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ).
cord-320928-flsaa1wx	2019	
cord-321080-pgxxkfc0	2019	We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. As shown in Figure 2 and Table 1 , combining HR2P-M2 and m336 resulted in strong synergistic inhibitory activity against MERS-CoV pseudovirus infection with CI values of 0.13-0.20 for 50-90% inhibition, including potency enhancement of 12.9-to 18.9-fold for m336 and 8.4-to 12.9-fold for HR2P-M2.
cord-321131-f8qeytxc	2015	Abstract In order to gain entry into cells, diverse viruses, including Ebola virus, SARS-coronavirus and the emerging MERS-coronavirus, depend on activation of their envelope glycoproteins by host cell proteases. We report here that the cysteine protease inhibitor K11777, ((2S)-N-[(1E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]-2-{[(E)-4-methylpiperazine-1-carbonyl] amino}-3-phenylpropanamide) and closely-related vinylsulfones act as broad-spectrum antivirals by targeting cathepsin-mediated cell entry. We report here that the cysteine protease inhibitor K11777, ((2S)-N-[(1E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]-2-{[(E)-4-methylpiperazine-1-carbonyl] amino}-3-phenylpropanamide) and closely-related vinylsulfones act as broad-spectrum antivirals by targeting cathepsin-mediated cell entry. Cell culture studies demonstrated that endosomal cysteine proteases, in particular cathepsin B (CTSB) and/or L (CTSL), can activate the glycoproteins of filoviruses, SARS-CoV, other coronaviruses, and NiV and Hendra (HeV) viruses to facilitate entry into certain cell lines. The notion that coronaviruses, including SARS-CoV, use both a cathepsin-dependent endosomal pathway and a direct cell-surface serine protease-mediated pathway for entry (Simmons et al., 2013) is supported by our finding that the combination of K11777 and camostat was superior to either compound alone.
cord-321185-kj67rd7g	2014	
cord-321259-wio2b49i	2020	Of note, cellular manipulation of autophagic levels during infection may also reflect desperate attempts of the cell to reestablish homeostasis, either through restriction of viral entry by actively shunting endocytosis/endosomal trafficking (possibly resulting in autophagy reduction as a sideeffect) [39] or to counteract virally induced cell death by increasing cytoprotective autophagy. Thus, the group-specific accessory proteins, which by definition are not essential for viral replication but are involved in the modulation of host cells and immune evasion [66, 67] , may represent targets for reducing the autophagy-inhibitory effects of CoVs. The FDA-approved anti-malarial drugs chloroquine and hydroxychloroquine have been suggested to be repurposed for the treatment of COVID-19 [68] [69] [70] , but this remains widely controversial [71] [72] [73] . Intriguingly, another recent preprint presents in vitro data showing that SARS-CoV-2 infection restricts autophagy and that, in turn, pro-autophagic compounds -including spermidine -may inhibit viral propagation [85] .
cord-321260-oi37dfsp	2017	
cord-321651-7e8dwcur	2020	This article describes the approach used to manage patients with cancer during a large-scale Middle East respiratory syndrome–coronavirus hospital outbreak in Saudi Arabia to ensure continuity of care and minimize harm from treatment interruption or acquiring infection. With recent outbreaks of the new coronavirus in China and other countries, the factors related to oncology patients'' care and corresponding outcomes are a major concern for the oncology community; therefore, this article describes the approach used to manage oncology services in response to the MERS-CoV outbreak and the implications of hospital closure. In coordination with the organizational leadership, the oncology service leaders developed a plan to manage the crisis with 3 main objectives: to treat affected patients, prevent further infection to patients and staff, and deliver timely, safe cancer care for all patients. In response to the 2015 coronavirus outbreak in our country, we developed a detailed plan to help manage oncology services to prevent harm to our patients or staff.
cord-321800-0h28pg3b	2020	
cord-321851-ku4z34lu	2020	
cord-321918-9jwma2y6	2020	The spike protein can be divided into two domains; S1 is responsible for angiotensin-converting enzyme II(ACE2) recognition, the recently identified host cell receptor, and S2 mediates membrane fusion (Figure 2 ). 98 99 On the basis of this approach, they identified two small molecules, TGG (12, Table 4 ) and luteolin (13) , that can bind avidly to the SARS-CoV S2 protein and inhibit viral entry of SARS-CoV into Vero E6 cells with IC 50 values of 4.5 and 10.6 μM, respectively. 113 A high-throughput screen (HTS) of a 1000-compound library that resulted in the identification of MDL28170 (17 , Table 4 ) by Bates et al., and in an antiviral activity assay, 17 specifically inhibited cathepsin L-mediated substrate cleavage and blocked SARS-CoV viral entry, with an IC 50 value of 2.5 nM and EC 50 value in the range of 100 nM.
cord-322354-x61eqaca	2020	A series of 4-anilino-6-aminoquinazoline derivatives were synthesized and evaluated to show high anti-MERS-CoV activities. N(4)-(3-Chloro-4-fluorophenyl)-N(6)-(3-methoxybenzyl)quinazoline-4,6-diamine (1) has been identified in a random screen as a hit compound for inhibiting MERS-CoV infection. [7] [8] [9] Recently outbreak of COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China and has spread to several other countries. Drug repositioning for an FDA-approved compound library found that numerous compounds inhibited MERS-CoV infection. 10 Through high content screening (HCS) platform of Institut Pasteur Korea (IPK) using the Korea Chemical Bank (KCB), 11 we found several novel compounds that can inhibit MERS-CoV infection. 12 We found that N 4 -(3-chloro-4-fluorophenyl)-N 6 -(3methoxybenzyl)quinazoline-4,6-diamine 1 was effective for inhibiting MERS-CoV infection. We thought that quinazoline compounds can exhibit good bioavailability and be easily extended to treatment of MERS-CoV infection. Middle East respiratory syndrome coronavirus (MERS-CoV)
cord-322760-tsxniu3j	2016	Thus, older age, pre-existing concurrent diseases, and delayed confirmation increase the odds of a fatal outcome in nosocomial MERS-CoV outbreaks in the Middle East and South Korea. Information on all laboratory-confirmed MERS cases was obtained from various publicly available sources, including WHO Global Alert and Response updates, documents officially released by the local health bureau, news releases from Middle Eastern and South Korean authorities, the Weekly Epidemiological Record, ProMed posts, and literature published from 1 April 2012 to 29 June 2016 (http:// www.who.int/csr/don/archive/disease/coronavirus_infections/ en/). In this study, we compared the mortality risk factors in two different nosocomial outbreaks, based on 51 nosocomial outbreaks of MERS-CoV infection in the Middle East and one large outbreak identified in South Korea. The severity of nosocomial outbreaks and the risk of fatal infection in HCP were significantly lower than the overall rate in the Middle East and South Korea. Middle East respiratory syndrome coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling
cord-323087-3cxyogor	2017	Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its receptor. Apart from dromedary camels, insectivorous bats are suggested as another natural reservoir for MERS-like-CoVs. In order to gain insight on the tropism of these viruses in bats, we studied the DPP4 distribution in the respiratory and extra-respiratory tissues of two frugivorous bat species (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat species (Pipistrellus pipistrellus and Eptesicus serotinus). The limited DPP4 expression in the respiratory tract of the two insectivorous bat species, particularly the common pipistrelle bat, is different from what has been reported for dromedary camels and humans. More importantly, the tissue distribution of DPP4 in insectivorous bats, believed to be one of the natural hosts for MERS-like-CoVs, is different to that in dromedary camels and humans.
cord-323093-u3ozc9ry	2020	After we observed that treatment with compound 6j resulted in the survival of MERS MA -CoV-infected hDPP4-KI mice, we conducted another study by delaying treatment initiation until 3 dpi. This nucleoside analog was originally developed as an antiviral drug against Ebola virus and has been shown to be effective against both MERS-CoV and SARS-CoV in cell culture assays and in animal models of coronavirus infection (23) (24) (25) (26) . Prophylactic treatment or early therapeutic treatment of infected mice with remdesivir reduced MERS-CoV-or SARS-CoV-mediated weight loss and decreased lung virus titers and lung injury scores compared to those of vehicle-treated animals (23, 26) . The goal of this study was to evaluate the efficacy of 3CLpro inhibitors against human coronaviruses, including SARS-CoV-2, in a FRET enzyme assay and cell culture assays, as well as in a mouse model of MERS-CoV infection.
cord-323125-qtlevnbt	2019	
cord-323428-jd91k19z	2019	
cord-323533-otosnjde	2020	After a broad screening of additional viruses, we now describe in vitro activity against Chikungunya virus (CHIK) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). These results led us to more broadly profile the antiviral spectrum of activity and focus on Chikungunya virus (CHIK) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). Plates are incubated at 37°C with 5% CO 2 until maximum CPE is observed microscopically in virus control wells (CHIK and MERS-CoV were incubated for 3 days). Tilorone has in vitro activity against CHIK and MERS-CoV. We identified promising micromolar activities for tilorone against CHIK and MERS-CoV with reasonable selectivity indexes ( Table 1 ). Recent virus outbreaks such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggest the urgent need for reassessment of this compound as a broadspectrum antiviral as we have yet to fully appreciate the utility of this drug discovered 50 years ago. Tilorone hydrochloride: an orally active antiviral agent Efficacy of tilorone dihydrochloride against Ebola virus infection
cord-324106-unvycvx4	2019	
cord-324165-afdmsbw2	2019	The results from regression models and sensitivity analyses demonstrated that areas with ≥100 SARS cases and closer proximity to the ROK had significantly larger percentage decreases in traveler volumes during the outbreak. This evaluation estimates the changes in numbers of non-citizen short-term visitor arrivals from selected areas to the ROK during the 2015 MERS outbreak and examines the correlation between travel volume declines and previous experience of the most similar sizable outbreak, the 2003 severe acute respiratory syndrome (SARS) outbreak. Although WHO did not recommend any travel restrictions to the ROK during the 2015 MERS outbreak [17] , WHO noted that raising awareness about Table 4 Monthly marginal percentage change between actual (2015) and baseline projected (average of 2013 and 2014) non-citizen arrivals to the Republic of Korea (ROK) associated with areas that experienced ≥100 probable severe acute respiratory syndrome (SARS) cases and distance to the Republic of Korea.
cord-324324-8ybfiz8f	2020	
cord-324671-7xdnmms9	2020	
cord-324926-3c5ab73l	2019	
cord-324978-9qfhsj3n	2014	
cord-325261-bdumhy5b	2020	
cord-325574-4zf9qtlh	2018	
cord-325902-33pxylb3	2019	This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. Experimental MERS-CoV infection in both alpacas and llamas showed a similar pattern to that of dromedary camels (Crameri et al., 2016; Vergara-Alert et al., 2017) , which suggested that both animals might act as a model animal for the study of MERS-CoV in vivo. Very few studies reported the cross-reactivity between MERS-CoV and other coronaviruses such as the bovine coronavirus (BCoV) that might infect dromedary camels. Dromedary camels remain the amplifier of the virus; the close contact of these animals to the human population in certain regions of Africa and Asia may pose a great risk for human infection and indirectly contribute to the spread of the virus. Lack of middle East respiratory syndrome coronavirus transmission from infected camels
cord-326133-d46wbfrx	2016	
cord-326718-jboiufoq	2020	In addition, three novel CoVs have emerged as zoonotic human infections in the past 17 years; SARS-CoV, Middle East respiratory syndrome CoV (MERS-CoV), and the 2019 novel CoV (SARS-CoV-2) (2) have each been associated with lower respiratory symptoms, progressing in a subset of individuals to acute respiratory distress syndrome (ARDS) and death. Interestingly NL63, an hCoV that also uses angiotensin converting enzyme 2 as the host receptor, but typically causes mild upper respiratory disease, was the cause of a cluster of severe pediatric pneumonias in China in 2018, during which half of the patients were identified with viruses containing a specific substitution in the spike glycoprotein that enhanced binding to and entry via angiotensin converting enzyme 2 (4). It can be hypothesized that the spike glycoprotein of SARS-CoV-2, with its PERSPECTIVE structural similarity and higher affinity binding to angiotensin converting enzyme 2, provokes a similar mechanism of lung pathology leading to ARDS with severe COVID-19.
cord-326768-uo6482ah	2019	The aim here was to screen symptomatic pilgrims for Middle East respiratory syndrome coronavirus (MERS‐CoV) and other viral etiologies. 2, [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] The emergence of the novel Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia, its endemicity, and high mortality rates (35%-40%) clearly represent another major public health concern, especially during Hajj. High prevalence of common respiratory viruses and no evidence of Middle East respiratory syndrome coronavirus in Hajj pilgrims returning to Ghana Detection of respiratory viruses among pilgrims in Saudi Arabia during the time of a declared influenza A(H1N1) pandemic MERS-CoV but positive influenza viruses in returning Hajj pilgrims, China Cross-sectional survey and surveillance for influenza viruses and MERS-CoV among Egyptian pilgrims returning from Hajj during 2012-2015. Middle east respiratory syndrome coronavirus (MERS-CoV) infections in two returning travellers in the Netherlands MERS-CoV, influenza and other respiratory viruses among symptomatic pilgrims during 2014 Hajj season
cord-326851-0jxdnm1l	2020	Results: Korea''s success rests on its readiness, with the capacity for massive testing and obtaining prompt test results, effective contact tracing based on its world-leading mobile technologies, timely provision of personal protective equipment (PPE) to first responders, effective treatment of infected patients, and invoking citizens'' community and civic conscience for the shared goal of defeating the pandemic. More specifically, this study has the following objectives: (1) To analyze Korean experiences with cases where healthcare facilities failed to prevent previous infectious diseases from spreading, and how these failures served the government in devising effective approaches to encounter the COVID-19 pandemic, (2) To dissect cases that showed innovative and successful response measures to deal with the COVID-19 pandemic, and (3) To elaborate on suggestions for crisis management based on the lessons learned from these COVID-19 response cases in Korea.
cord-326864-i1r3bv4p	2020	4 COVID-19 is a respiratory tract infection that causes mild symptoms in the majority of cases, but can also lead to ISSN: 1740-4398 REVIEW -Coronavirus disease 2019 : latest developments in potential treatments drugsincontext.com mortality and morbidity. SARS-CoV is closely related to civet and bat CoVs, but it is phylogenetically divergent from other coronaviruses associated with human infections, including ISSN: 1740-4398 REVIEW -Coronavirus disease 2019 (COVID-19): latest developments in potential treatments drugsincontext.com OC43, NL63, 229E, and HKU1. In a clinical trial involving 199 patients with laboratory-confirmed SARS-CoV-2 infection, lopinavir-ritonavir treatment was not associated with any clinical improvements compared with standard care. 25 Long and colleagues reported that corticosteroid therapy using methylprednisolone, dexamethasone, and hydrocortisone was beneficial in treating ISSN: 1740-4398 REVIEW -Coronavirus disease 2019 (COVID-19): latest developments in potential treatments drugsincontext.com SARS-CoV patients, 78 and significantly prolonged survival time in clinical cases.
cord-327063-ea7a1xfl	2020	
cord-327685-fymfqvp3	2017	In contrast, highly pathogenic hCoVs such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) predominantly infect lower airways and cause fatal pneumonia. Severe pneumonia caused by pathogenic hCoVs is often associated with rapid virus replication, massive inflammatory cell infiltration and elevated pro-inflammatory cytokine/chemokine responses resulting in acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Although there is no direct evidence for the involvement of pro-inflammatory cytokines and chemokines in lung pathology during SARS and MERS, correlative evidence from patients with severe disease suggests a role for hyper-inflammatory responses in hCoV pathogenesis. Infection of non-human primates (NHPs) with SARS-CoV induced a dysregulated immune response resulting in increased disease severity in aged but not young NHPs, despite similar viral titers in the airways [67] . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice
cord-327863-6cw9f7qu	2015	As of July 15, 2015, the South Korean Ministry of Health and Welfare had reported 186 case-patients with Middle East respiratory syndrome in South Korea. For 159 case-patients with known outcomes and complete case histories, we found that older age and preexisting concurrent health conditions were risk factors for death. Univariate logistic regression models for each risk factor showed that older age and having a concurrent health condition were associated with death (both p<0.001); both variables remained significant after we adjusted for all 5 variables in a multivariate logistic regression model (Table) . Despite these limitations, we found that risk factors for death among patients with MERS in South Korea who had known outcomes (age and concurrent health conditions) were similar to those identified for MERS case-patients in Saudi Arabia (8) (9) (10) .
cord-327867-1wkbjtji	2018	title: Underlying trend, seasonality, prediction, forecasting and the contribution of risk factors: an analysis of globally reported cases of Middle East Respiratory Syndrome Coronavirus This study set out to identify and analyse trends and seasonal variations of monthly global reported cases of the Middle East respiratory syndrome coronavirus (MERS-CoV). This study set out to identify trends and seasonal variations; made a prediction based on the globally reported cases of the Middle East respiratory syndrome coronavirus (MERS-CoV), extrapolated into the future by forecasting the trend and assessed contributions of various risk factors for the MERS-CoV cases. Using linear time series models and their application to the modelling and prediction of the globally reported MERS-CoV data, the present study identified trends, analysed seasonality, predicted and forecast evolution of MERS-CoV cases and assessed the contribution of various risk factors.
cord-328000-i9tzr13z	2018	
cord-328175-4i3cz20j	2017	Abstract Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Here we assess the effect of treatment with marmoset-derived hyperimmune plasma as well as the human mAb m336 on disease outcome in the recently developed marmoset MERS-CoV infection model, which recapitulates severe respiratory disease (Falzarano et al., 2014) . Viral loads in lung tissues from hyperimmune plasma-treated compared to control animals were found to be significantly lower using a onetailed unpaired Student''s t-test (average of 4.0 Â 10 4 and 1.2 Â 10 6 TCID 50 equivalent/gram, respectively, p-value ¼ 0.008). In this study, hyperimmune plasma treatment of marmosets inoculated with MERS-CoV resulted in a small (0.5e1 log) but significant reduction in respiratory tract viral loads, as well as reduced disease severity such as observed with radiographs, compared to marmosets treated with non-convalescent plasma or PBS.
cord-328298-tm7gds8h	2016	In order to prevent global outbreaks such as the one seen in South Korea, it is critical for high-risk countries to be prepared and have appropriate screening and triage protocols in place to identify travel-related cases of MERS-CoV. The results provide a country level ranking and corresponding expected relative risk, which can be used by public health authorities in each country to ensure the appropriate screening and triage protocols are in place to identify travel-related cases of MERS-coronavirus. The proposed model quantifies the relative risk of disease spread by MERS-CoV-infected travellers departing from the Middle East and arriving at any given world airport. The analysis quantifies the relative expected risk of MERS-CoV-infected (air travel) passengers arriving at airports based on a set of active transmission regions, the outbreak size at each and travel patterns; the model does not include the potential importation of infected intermediary hosts or intermediary host by-products since the influence of that possibility is yet to be established.
cord-328361-hyrke6j2	2013	A novel clade 2c betacoronavirus, termed Middle East respiratory syndrome (MERS)-CoV, was recently identified as the causative agent of a severe respiratory disease that is mainly affecting humans on the Arabian Peninsula (1) . Extending on previous work (2), we described European Pipistrellus bat-derived CoVs that are closely related to MERS-CoV (3) . Screening for CoVs was done by nested reverse transcription PCR using broadly reactive oligonucleotide primers targeting a conserved region in the RNA-dependent RNA polymerase (RdRp) gene (online Technical Appendix). PCR amplicons for 4 positive specimens yielded alphacoronavirus sequences related to recently described bat alphacoronaviruses from South Africa (4) . A Bayesian phylogenetic analysis of the 816-nt RdRp sequence confirmed the close relationship between PML/2011 and MERS-CoV (Figure) . Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences
cord-328366-new4d9jg	2017	title: Delayed management of Staphyloccocus aureus infective endocarditis in a Middle East respiratory syndrome coronavirus possible case hospitalized in 2015 in Paris, France The risk of emerging infectious diseases such as Middle East respiratory syndrome coronavirus (MERS-CoV) [1] and Ebola epidemics is growing not only as the result of changes in demographic, anthropological, ecological and economic conditions but also because of increasing connectedness and speed of movement in the modern world. In France, since 2012, 1524 patients were classified as possible cases, two were confirmed as MERS-CoV infection, of which one died [4] . A man in his sixties with possible MERS-CoV was admitted to our infectious diseases department at Bichat Claude Bernard Hospital in Paris in 2016. Twelve hours after admission (H12), based on the infectious disease clinical assessment, MERS-CoV diagnosis was no longer considered. Here, the suspicion of MERS-CoV led to a 12-hour delay in performing blood cultures because of isolation.
cord-328835-r9znjkfo	2020	
cord-329010-n0mz098o	2020	Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may prevent spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic. Drugs that have recently been shown to target MERS-CoV in mice [15] , and to inhibit Ebola virus RdRP and SARS-CoV-2 proteases in humans, such as remdesivir and ritonavir/lopinavir, also constitute candidate drugs against SARS-CoV-2 and are now investigated for their therapeutic efficacy in COVID-19 patients in 2 international clinical trials (SOLIDARITY Trial and DisCoVeRy Trial). The emergence of the novel beta coronavirus SARS-CoV-2 from Wuhan, Hubei province, China in December 2019 rapidly led to a pandemic involving more than 2,500,000 infected persons and more proven drugs such as camostat mesilate which prevents virus host cell entry by inhibiting TMPRSS2 [8] , and chloroquine phosphate which inhibits terminal phosphorylation of ACE2, or hydroxychloroquine which is metabolized in vivo to chloroquine [44] .
cord-329190-kv9n2qj3	2017	
cord-329876-4cgrjnjo	2016	title: Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin To contribute to an understanding of this process, we present here the X-ray crystal structure of a complex between MERS-CoV PL(pro) and human ubiquitin (Ub) that is devoid of any covalent linkage between the two proteins. The substrate-binding site of MERS-CoV PL pro features significant differences from those of the corresponding SARS-CoV enzyme and human ubiquitin-specific proteases (USPs, such as, USP14) (Hu et al., 2005; Chou et al., 2014; Ratia et al., 2014) . Hence, we crystallized the ubiquitin (Ub) complex of a MERS-CoV PL pro variant that had the active-site Cys111 replaced by serine (C111S) and determined the structure at 3.16 Å ( Figure 1A ). Crystal structure of the Middle East respiratory syndrome coronavirus (MERS-CoV) papain-like protease bound to ubiquitin facilitates targeted disruption of deubiquitinating activity to demonstrate its role in innate immune suppression
cord-329959-4yecwdlo	2017	Here we show that a clinically available alcohol-aversive drug, disulfiram, can inhibit the papain-like proteases (PL(pro)s) of MERS-CoV and SARS-CoV. The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PL(pro) by disulfiram, while synergistic inhibition of MERS-CoV PL(pro) by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs. For the inactivation studies, SARS-CoV PL pro (0.05 μM in 20 mM phosphate buffer, pH 6.5) was incubated with different concentrations of disulfiram and peptide substrate, and enzymatic activity was traced for 5 min. On the other hand, the results of kinetic assays, continued inactivation after the removal of disulfiram, reactivation by reductant, and the phenomenon of slow-binding inhibition suggest that disulfiram may act at the active site of SARS-CoV PL pro , forming a covalent adduct with residue Cys112.
cord-330315-upcf15q5	2017	
cord-330343-p7a8chn4	2019	► Diagnostic research and development (R&D) needs to include point-of-care testing options, syndromic panels for differential diagnosis, a greater understanding of viral and antibody kinetics, improved access to clinical specimens, and establishment of international reference standards. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation.
cord-330583-ltkpt80u	2019	Following the 2003 the severe acute respiratory syndrome (SARS) and the 2015 Middle East Respiratory Syndrome (MERS) outbreak in South Korea, this research aims to explore and examine the factors influencing the response to infectious diseases, which encompasses both communicable and non-communicable diseases. As the results conducted meta-analyses to comprehensively analyze the correlations of factors influencing disaster response from a Korean context, the findings show that the legislative factor had direct and indirect influence on the overall process of infectious disease response and that Leadership of the central government, establishment of an intergovernmental response system, the need for communication, information sharing and disclosure and onsite response were identified as key factors influencing effective infectious disease response. However, there is also need for comprehensive discussions that include the establishment of laws; regulations; resources; information on infectious disease response from administrative and policy perspectives; information sharing system; and the establishment of an international cooperation system and national response system involving the central government, the regional government, private organizations and the public for effective response when an actual infectious disease outbreak occurs.
cord-330913-8aezw81h	2020	This study reviewed the state-of-the-art techniques for CoV prediction algorithms based on data mining and ML assessment. The main contributions of this study are the exploration of the CoV family by reviewing articles on data mining and ML algorithms, the acquisition of a clear understanding of its enhancements, and how previous research has addressed prediction, regression, and classification methods. Given the multidisciplinary topic of this systematic review, data extraction and classification of the selected studies, including data concerning CoV with AI applications (especially ML techniques), were conducted to evaluate the efficacy of this virus in terms of detection, diagnosis and classification throughout AI enhancements. In [8] , a study was conducted in Saudi Arabia between 2013 and 2017 to improve medical diagnosis systems for binary and multiclass problems in MERS-CoV datasets. In [16] , data mining based on statistical methods was utilised to develop a cloud-based medical system with a high prediction accuracy to prevent MERS-CoV spread within different regions.
cord-331022-tek4u751	2020	
cord-331228-wbd0s4fo	2016	
cord-331558-6rqd3fmj	2020	Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct and share the same entry receptors for some respiratory viruses, the eye is rarely involved in human CoV infection, conjunctivitis is quite rare in patients with 2019-nCoV infection, and the CoV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with 2019-nCoV and SARS-CoV infection is also extremely low. Considering that close doctor-patient contact is quite common in ophthalmic practice and is apt to transmit human CoVs via droplets and fomites, strict hand hygiene and proper personal protection are highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice. Considering that close doctor-patient contact is quite common in ophthalmic practice and is apt to transmit human CoVs via droplets and fomites, strict hand hygiene and proper personal protection are highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.
cord-331980-m6dflwmm	2016	
cord-332237-8oykgp0h	2014	
cord-332268-x30svp5y	2020	
cord-332952-d5l60cgc	2018	Typical of an emerging zoonosis, Middle East respiratory syndrome coronavirus (MERS-CoV) has an animal reservoir, i.e. dromedary camels in which the virus causes little to no disease (Mohd et al., 2016) . For example, studies of respiratory pathogens (Yu et al., 2007; Tran et al., 2012; Thompson et al., 2013) and MERS-CoV conducted in the Middle East (Assiri et al., 2013; Oboho et al., 2015; Hunter et al., 2016; Balkhy et al., 2016) and the Republic of Korea (Bin et al., 2016; Kim et al., 2016a Kim et al., , 2016b Nam et al., 2017) illustrate that aerosol-generating procedures and non-invasive ventilation, combined with inappropriate infection prevention and control practices and lack of adherence to standard practices had an important role in facilitating human-to-human transmission in health care settings. The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study Sero-prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) specific antibodies in dromedary camels in Tabuk, Saudi Arabia
cord-333144-gyuh2fvl	2020	
cord-333606-5z3kumu9	2020	title: Coronaviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines In this review, we focus on our present understanding of innate immune responses, inflammasome activation, inflammatory cell death pathways, and cytokine secretion during SARS-CoV, MERS-CoV, and SARS-CoV-2 infection. Despite these limitations, significant work has been done to molecularly characterize the innate immune pathways involved in detecting and controlling CoV infections. patients with severe or critical COVID-19 also found that reduced amounts of type I IFNs in the blood during SARS-CoV-2 infection were associated with increased viral load in the blood, and exacerbation of the inflammatory response [38] . Pyroptosis and necroptosis are similar in that they are lytic forms of cell death driven by the GSDMD pore and MLKL channel, respectively, that release proinflammatory cytokines and other cellular factors to alert the surrounding cells of danger and to recruit innate and adaptive inflammatory cells [54, 55].  Specific CoV infections can activate inflammatory cell death (PANoptosis), thereby inducing cytokine release.
cord-333738-3xtb8gye	2020	Investigating patient serum samples after SARS-CoV-2 infection in cross-reactivity studies of immunogenic peptides from Middle East respiratory syndrome coronavirus (MERS-CoV), we were able to detect the production of antibodies also recognizing MERS virus antigens. Indeed, the peptide of the HR2 domain of the MERS spike protein, previously proven to induce antibodies against MERS-CoV is sharing 74% homology with the corresponding sequence of SARS-CoV-19 virus. If used as an antigen, the peptide of the HR2 domain of the MERS spike protein allows discrimination between post-Covid populations from non-infected ones by the presence of antibodies in blood samples. The high homology of the spike protein domain suggests in addition that the opposite effect can also be true: coronaviral infections producing cross-reactive antibodies affective against SARS-CoV-19. SARS-CoV-2 infections results in the generation of antibodies with significantly strong cross-reactive towards a MERS specific peptide with 76% homology. Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein
cord-333882-zrdsr3nh	2018	
cord-334530-krclgmc4	2014	title: Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections, Tunisia, 2013 In 2013 in Tunisia, 3 persons in 1 family were infected with Middle East respiratory syndrome coronavirus (MERS-CoV). The index case-patient''s respiratory tract samples were negative for MERS-CoV by reverse transcription PCR, but diagnosis was retrospectively confirmed by PCR of serum. A s of May 23, 2014, a total of 635 laboratory-confirmed human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infections had been reported to the World Health Organization; the epidemic has subsequently accelerated (1) . Nasopharyngeal and/or throat swab samples were Family Cluster of MERS-CoV Infections, Tunisia collected a mean of 5 weeks after contact from the other 2 (not ill) children of patient 1, his spouse, and the spouse of patient 3. Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission
cord-334628-axon4jdc	2017	In this study, bat samples (332 oral swabs, 245 fecal samples, 38 urine samples, and 57 bat carcasses) were collected at 33 natural bat habitat sites in South Korea. Thirteen sequences belonging to SARS-like betacoronaviruses showed the highest nucleotide identity (97.1–99.7%) with Bat-CoV-JTMC15 reported in China. Given the import of MERS into South Korea [14] and the presence of SARS in the relatively close geographic location of China [9] (Fig. 3) , together with the fact that bats are a reservoir for coronaviruses, the prevalence of coronavirus infection in Korean bat species should provide valuable information. Oral swabs and other samples (n = 60) were obtained from three species of bats, Rhinolophus ferrumequinum, Miniopterus schreibersii, and Myotis macrodactylus, but coronaviruses were only detected in samples from R. Thirteen sequences from oral swabs were clustered with Bat-CoV B15-21, which was detected in fecal bat samples collected from an abandoned mine in Gangwon province.
cord-334667-0cah15lg	2020	
cord-334738-k6002qzb	2016	
cord-334960-l5q5wc06	2020	9) Two novel strains of coronavirus have jumped species from animal to human, spread by human-to-human transmission, and caused severe acute respiratory syndrome leading to high fatality rate in the past 2 decades. 10) Severe acute respiratory syndrome-associated virus (SARS-CoV), previously unknown coronavirus traced to horseshoe bats in southern China, caused 8,096 confirmed cases and 774 deaths (9.6% fatality rate) in 29 countries from November 2002 to July 2003. 19, 20) The virus was initially called 2019-novel coronavirus (2019-nCoV) upon its emergence, until the Coronaviridae Study Group of International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) based on the phylogenetic analysis, on February 11, 2020. 10) Conclusion Within 3 months since the discovery of a novel coronavirus in patients with pneumonia of unknown origin in Wuhan City, China, COVID-19 has spread rapidly throughout the world and is beating SARS-CoV and MERS-CoV in the number of confirmed cases and deaths.
cord-335567-ssnvr6nj	2015	
cord-336150-l8w7xk0b	2020	The essential surface glycoprotein of SARS-CoV-2 known as spike (S) protein, essential for host cell receptor binding, showed only 72% similarity with SARS-CoV at the nucleotide level. Comparative genome analysis of RaTG13, a virus from a Rhinolophusaffinis (i.e. horseshoe) bat sampled from Yunnan province in China in 2013, with SARS-CoV-2, showed that SARS-CoV-2 has 96% similarity at the nucleotide sequence level . Later, it was found that the disease was caused by a virus designated as a novel human coronavirus, MERS-CoV, phylogenetic data showed that it belonged to lineage C of the Betacoronavirusgenus and was highly similar to bat coronaviruses HKU4 (Tylonycterispachypus) and HKU5 (Pipistrelluspipistrellus; Lau et al. When cell lines over-expressed the transmembrane protein ''angiotensin-converting enzyme 2'' (ACE2) from humans, bats, pig or civet cats and were infected with SARS-CoV-2, results showed that they became hypersensitized to infection, thus indicating that ACE2 is a SARS-CoV-2 receptor . Recently, neutralizing monoclonal antibodies and nanobodies against the RBD domain of S protein showed protection against SARS-CoV and MERS-CoV (Du et al.
cord-336775-d4hi9myk	2020	Abstract Human Coronaviruses (HCoV), periodically emerging across the world, are potential threat to humans such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) – diseases termed as COVID-19. Hence, acute respiratory distress syndrome (ARDS) is caused by cytokine storm that triggers a destruction in host cells via immune system and subsequently results into multiple organs failure or death as stated in case of SARS-CoV-2 outbreak; similar observations were noted in case of SARS-CoV infection (Kumar et al., 2020) . When developing novel therapeutic strategies to check the immunoregulatory cytokines such as TNFβ and IL6, investigation should be considered on the viral strain and targeted organ specificity; for example, SARS-CoV-2 has more affinity to ACE2 which are scattering on different organs like lung and kidney while MERS-like CoV can even infect T-cells. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)
cord-337066-pztrwvib	2016	
cord-337089-ksh62ni0	2020	
cord-337499-jzpgtkai	2020	
cord-337825-ujq9mxk7	2020	
cord-337835-78i6j11i	2017	
cord-338057-ycmr9prw	2015	
cord-338436-0z828org	2020	
cord-338538-uea9kwge	2019	
cord-338564-68z2pxfz	2016	
cord-338776-2wa30218	2020	The cytokine and/or chemokine induction was significantly attenuated by siRNA depletion of retinoic acid-inducible-I-like receptors (RLR) or adaptor, indicating that RLR signaling also contributed to MERS-CoV-induced proinflammatory response. We first used the inhibitors of RLR and CLR signaling pathway to evaluate their potential contribution for mediating the proinflammatory response in MERS-CoV-infected macrophages. To assess the contribution of RLR or CLR pathway to induce proinflammatory response, we measured the expression levels of a series of key proinflammatory cytokines and/or chemokines in MERS-CoV-infected MDMs in the presence of these inhibitors ( Figure 1B ). Overall, the above results suggested that RLR and CLR signaling might be involved in viral recognition and trigger the proinflammatory response upon MERS-CoV infection in macrophages. Our results indicate that CLR and RLR signaling may be involved in mediating the immune activation in MERS-CoV-infected human macrophages.
cord-338973-73a7uvyz	2020	After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The source of unexplained pneumonia was first discovered in Wuhan in Dec, 2019, and SARS-CoV-2, a new coronavirus, was isolated from the respiratory epithelium of patients. Hong Kong scholars found that, compared with ribavirin alone, patients treated with lopinavir/ritonavir and ribavirin had lower risk of acute respiratory distress syndrome (ARDS) or death caused by SARS-CoV [76, 77] . A high-resolution crystal structure of SARS-CoV-2 coronavirus 3CL hydrolase (Mpro) was announced after the outbreak of COVID-19 in the world [80] , and human coronaviruses (HCoVs) have been treated as severe pathogens in respiratory tract infections.
cord-338980-pygykil7	2016	
cord-339146-ifdgl2bj	2016	During investigation of a multi‐facility outbreak of MERS‐CoV in Taif, Saudi Arabia, we identified a mixed population of wild‐type and variant sequences with a large 530 nucleotide deletion in the spike gene from the serum of one patient. Serum specimens from Taif patients were screened for MERS-CoV by real-time RT-PCR and positive samples were further subjected to RT-PCR and Sanger sequencing of the spike gene as previously reported [Assiri et al., 2016a] . As previously reported [Assiri et al., 2016a] , realtime RT-PCR testing of serum specimens from a MERS-CoV outbreak in Taif identified two epidemiologically linked case-patients (#27 and #30) with identical spike gene sequences. Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia
cord-339152-wfakzb6w	2020	Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. The occurrence of significant disease outbreaks-such as SARS (severe acute respiratory syndrome) originating in China in 2002 (8) , the 2009 H1N1 swine flu pandemic from Mexico (9) , MERS (Middle East respiratory syndrome) that occurred in Saudi Arabia in 2012 (10) , the West African outbreak of Ebola virus (EBOV) in late 2013 (11) , the Zika virus (ZIKV) outbreak originating in Brazil in 2015 (12) , the 2018 health emergence in Nigeria caused by Lassa virus (13) , and the ongoing Coronavirus disease 2019 (COVID19) pandemic (14) -has renewed interests in developing strategies to faster prevent, treat, and/or control emerging and re-emerging viruses with high epidemic potential.
cord-339386-sxyeuiw1	2015	
cord-339724-roj8ksvc	2014	title: Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. In this study, different adjuvants combination regimens including alum, IFA, CpG and poly(I:C) were compared in an effort to promote balance between Th1 and Th2 immune response to bystander rRBD antigen spanning residues 367-606 of MERS-CoV S in a murine model to develop an effective vaccine against MERS-CoV infection. The results indicated that rRBD protein combined with any adjuvant, including alum, IFA, CpG or poly(I:C), could induce a RBD-specific IgG antibody response in the majority of mice after the second immunisation.
cord-339762-lh8czr0a	2016	title: Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014 Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a sputum specimen of a patient who died of respiratory and renal failure in Saudi Arabia in 2012. Although the pathogenesis of severe and fatal MERS-CoV infection is unknown, these postmortem findings provide critical insights, including evidence that pneumocytes are important targets, suggesting that direct cytopathic effects contribute to MERS-CoV respiratory symptoms.
cord-340163-ex03l0pc	2020	
cord-340836-eb5a9ln3	2018	METHODS: Full details of MERS-CoV cases available on the disease outbreak news section of the World Health Organization official website from January 2013 to November 2016 were retrieved; demographic and clinical information, global distribution status, potential contacts, and probable risk factors for the mortality of laboratory-confirmed MERS-CoV cases were extracted and analyzed by following standard statistical methods. From September 23, 2012, to November 11, 2016, the occurrence of 1,879 laboratory-confirmed cases of MERS-CoV infection, including 659 deaths, was reported to WHO by the National IHR Focal Points of 27 countries in Europe, North Africa, the Middle East, the United States of America, and Asia. The comparison of characteristics of the cases and the effect of various potential risk factors on the final outcome (dead/survived) of laboratory-confirmed MERS-CoV cases in the world (Table 2) reveal that two factors, namely, morbid case being native and travel history, are considered significant in a unifactorial analysis (P-values are <0.05) and with the potential of bearing on the dynamics of the disease.
cord-341056-iwu428pk	2020	
cord-341620-nmrkhx5t	2020	
cord-341698-k5leys8j	2016	In the early summer of 2015, Middle East respiratory syndrome (MERS) struck South Korea, and students of Sungkyunkwan University School of Medicine (SKKUSOM) were at risk of contracting the disease. METHODS: Through a process of reflection-on-action, we examined SKKUSOM''s efforts to avoid student infection during the MERS outbreak and derived a few practical guidelines that medical schools can adopt to ensure student safety in outbreaks of infectious disease. Five suggestions are extracted for medical schools to consider in infection outbreaks: instant cessation of clinical clerkships; rational decision making on a school closure; use of information technology; constant communication with hospitals; and open communication with faculty, staff, and students. Through a process of reflection-on-action [6] , we identified the necessary actions taken to ensure student safety and derived practical guidelines that medical schools can take to protect students in the face of outbreaks of infectious disease.
cord-341795-zbqfs77n	2019	This systematic review aims to compile and analyse all published data on MERS-coronavirus (CoV) in the global camel population to provide an overview of current knowledge on the distribution, spread and risk factors of infections in dromedary camels. In the field surveys included in this review, MERS-CoV RNA has been described in rectal swab samples, although other field studies report negative results [3, [22] [23] [24] and when viral RNA can be detected, the positivity rate of rectal swabs is lower compared with nasal swab samples [19, [25] [26] [27] . Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study Longitudinal study of Middle East respiratory syndrome coronavirus infection in dromedary camel herds in Saudi Arabia Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels
cord-342052-v4y1xc90	2017	
cord-342144-awtiqxx5	2020	Ein klinischer Nutzen konnte beim Einsatz der eigentlich für die Behandlung von Humane-Immundefizienz(HIV)-Infektionen verwendeten Proteaseinhibitoren Lopinavir und Ritonavir (Kaletra ® ) zur Therapie des SARS-CoV nachgewiesen werden [6] . Im Dezember 2019 trat in China erstmalig ein neues Coronavirus auf, das zunächst als 2019-nCoV bezeichnet wurde und nach aktueller Nomenklatur des International Committee on Taxonomy of Viruses (ICTV) nun als SARS-CoV-2 bezeichnet wird [7] . So ist der kombinierte Einsatz der Proteaseinhibitoren Lopinavir und Ritonavir bei SARS-CoV-Patienten von klinischem Nutzen [6] . Eine weitere Studie mit MERS-CoV-Infizierten wird in Saudi-Arabien durchgeführt, bei der mit Lopinavir/Ritonavir plus Interferon-β behandelt wird [30] ; Daten zu den Ergebnissen liegen noch nicht vor. konnte gezeigt werden, dass die zelluläre Protease TMPRSS2 für die Infektiosität von SARS-CoV-2 essenziell ist und eine Hemmung dieser Protease mithilfe von Camostat-Mesilat die Vermehrung des Virus u.
cord-342691-8jcfzexy	2020	Among a series of novel use cases, we gather evidence for hypotheses that SARS2 infection efficiently represses E2F family HCTs encoding key drivers of DNA replication and the cell cycle; that progesterone receptor signaling antagonizes SARS2-induced inflammatory signaling in the airway epithelium; and that SARS2 HCTs are enriched for genes involved in epithelial to mesenchymal transition. Here, as a service to the research community to catalyze the development of novel CoV therapeutics, we generated consensomes for infection of human cells by MERS, SARS1 and SARS2 CoVs. Computing the CoV consensomes against those for a broad range of cellular signaling pathway nodes, we discovered robust intersections between genes with high rankings in the CoV consensomes and those of nodes with known roles in the response to CoV infection. To enable researchers to routinely generate mechanistic hypotheses around the interface between CoV infection human cell signaling, we next made the consensomes and accompanying HCT intersection analyses freely available to the research community in the SPP knowledgebase and the Network Data Exchange (NDEx) repository.
cord-342739-iy9vjpuh	2020	In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. The most common adverse obstetrical outcomes associated with maternal pneumonias from all causes include This newly recognized coronavirus, producing a disease that has been termed COVID-19, is rapidly spreading throughout China, has crossed international borders to infect persons in neighboring countries, and humans infected by the virus are travelling via commercial airlines to other continents. Pregnant women may develop severe disease and fatal maternal and/or fetal outcomes as a result of MERS-CoV infection; however, little is known of the pathophysiology of this infection during pregnancy.
cord-342756-rgm9ffpk	2020	Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. In the following topic, we will review SARS-CoV-2 structure and mechanism of infection in order to discuss molecular targets from the virus or its human host that are being considered for drug repurposing and perhaps future development of new drugs. (128) Its role as a functional receptor of SARS-CoV-2 S protein in host cells makes this protein a potential drug target to treat COVID-19. (138) TMPRSS2 has a major role in SARS-CoV-2 cell entry and replication, and thus represents an interesting therapeutic target since its inhibitors could potentially block virus infection in its initial stages. (199) A robust preclinical drug discovery pipeline comprising in vitro, and in vivo models of SARS-CoV-2 infection is particularly important to identify new antivirals for human COVID-19 treatment.
cord-343107-oj1re34k	2019	
cord-343184-kptkmgdm	2016	title: Experimental Infection and Response to Rechallenge of Alpacas with Middle East Respiratory Syndrome Coronavirus We conducted a challenge/rechallenge trial in which 3 alpacas were infected with Middle East respiratory syndrome coronavirus. However, the alpaca, a close relative within the Camelidae family, may provide a temperamentally suitable and valuable animal model for MERS-CoV infection, particularly for developing and testing vaccine candidates for camels. We found no previous MERS-CoV challenge trial reported in alpacas, so we chose a preliminary dose and rechallenge time on the basis of our experience with other virus infection trials for other emerging infectious diseases (8) . Our challenge/rechallenge trial was planned as a first stage in the assessment of the alpaca as a potential surrogate for camels for MERS-CoV vaccine testing. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study Infection, replication, and transmission of Middle East respiratory syndrome coronavirus in alpacas
cord-343196-vlwzzrgc	2018	The MERS-CoV RNA-positive animals belonged to two different dromedary camel herds in Dabel and Lombolio, which are both located within Isiolo country. To experimentally confirm the presence of two independently circulating MERS-CoV strains and to rule out sample cross-contamination, we generated complete MERS-CoV genome sequences using a previously established protocol 10 . Other confirmed MERS-CoVpositive samples were assigned to two different MERS-CoV isolates ("Dabel" or "Lombolio") by amplifying and sequencing single-nucleotide polymorphisms in the spike gene and the open reading frame 3 (Supplementary Table) . The previously described clade C African MERS-CoV strains 4,5 had several mutations in the spike protein, which is responsible for cellular receptor interaction, virus entry, and antibody-directed virus neutralization 12 . An explanation for this observation may again be a lack of testing of imported animals and/or the fact that previous clade A/B MERS-CoV infections may have established herd immunity in the Arabian dromedary populations.
cord-343302-g9vcchrh	2016	
cord-343528-5283jsnu	2016	
cord-343789-6tq0kcfd	2014	
cord-344217-kci4uw7u	2020	
cord-344246-sf9cymhc	2020	Previous outbreaks of coronaviruses include the severe acute respiratory syndrome (SARS)-CoV epidemic in 2003 [2] and the Middle East respiratory syndrome (MERS)-CoV in 2012 [3] , while the newly emergent coronavirus, initially referred to as 2019-nCoV and subsequently termed SARS-CoV-2, the disease it produces has been termed COVID-19, which causes respiratory infection and can progress to severe pneumonia and, in a small number of cases, death [4] . A systematic review and meta-analysis was aimed to assess the effect of coronavirus infection (SARS-CoV-2, MERS-CoV, and SARS-CoV) during pregnancy and its possibility of vertical maternal-fetal transmission following the methodological framework suggested by Arksey and O''Malley [15] . The primary outcome variable of this study was the pregnancy outcomes observed, listed as follows: preterm birth (PTB; either before 37 or 34 weeks of gestation), preeclampsia, preterm prelabor rupture of membranes, (pPROM), fetal growth restriction (FGR), miscarriage, maternal death, mode of delivery and other clinical feature, laboratory findings and coexisting disease. An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: maternal coronavirus infections and pregnancy outcomes
cord-344330-zsx7wfyj	2016	
cord-344954-gpb25fga	2019	
cord-345046-str19r9a	2016	title: Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia In this recent cohort, when comparing survivors to nonsurvivors, survival was associated with male gender, vomiting on admission, elevated respiratory rate, abnormal lung exam on physical exam, working as a healthcare worker, history of hypertension, elevated ALT, clearance of MERS CoV on repeat PCR testing, and receiving mycophenolate mofetil or beta interferon (Table 1 ). In analyzing the relationship between severity of illness and treatments administered, beta interferon and mycophenolate mofetil were given to less severely ill patients (Table 3) Discussion MERS-CoV is an emerging disease for which the initial epidemiology has been described, but in-depth clinical studies and the role of therapy in incompletely understood. We present data from a retrospective cohort of ill patients with Mers-CoV and the results of the evaluation of the clinical efficacy of beta interferon beta, alpha interferon, ribavirin and mycophenolate mofetil in addition to routine supportive care.
cord-345081-15s2i6f0	2017	As of January 2016, 1,633 laboratory-confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection and 587 MERS-related deaths have been reported by the World Health Organization globally. Middle East Respiratory Syndrome Coronavirus may also spread through aerosols generated during various dental treatments, resulting in transmission between patients and dentists. 1, 17 Viral infections, such as severe acute respiratory syndrome Saudi Med J 2017; Vol. 38 (4) www.smj.org.sa (SARS-CoV), may be transmitted to healthcare workers from infected patients through aerosols. 19 This review is an attempt to discuss MERS-CoV infection among children and those providing dental treatment to them, including precautions and considerations pertaining to the practice of pediatric dentistry. In pediatric dental practice, effective infection control measures for the prevention or minimization of viral infection transmission can be implemented by a) controlling the gag or cough reflex; b) reducing aerosol/ splatter generation; c) managing contaminated air and; d) improving personal protection.
cord-345591-zwh1xj5u	2016	title: The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August–September 2015). Eight HCWs had MERS requiring ICU admission (median stay = 28 days): Seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. The Middle East respiratory syndrome (MERS) coronavirus is a recently identified virus that is closely related to the severe acute respiratory syndrome coronavirus (SARS-CoV) [1] , causes severe hypoxemic respiratory failure with multiorgan failure and frequently requires admission to the intensive care unit (ICU) [2, 3] .
cord-345827-yo3uq03v	2020	
cord-346320-ysgz6adr	2016	
cord-346331-d0s028wl	2020	Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. • Limited, weak evidence suggests that some coronaviruses (including SARS-CoV-2) may be present in human milk, but these studies do not report methods of sample collection and validation of reverse transcription polymerase chain reaction (RT-PCR) assays for human milk. Of particular interest in this context are (1) the potential role that breastfeeding could play in vertical transmission of SARS-CoV-2 from women to infants via human milk and (2) the potential protective effects of targeted antibodies and other immunoprotective components in human milk against COVID-19. Milk was submitted to the CDC, where it was analysed using reverse transcription polymerase chain reaction (RTSearch terms, databases and preprint servers used to identify existing literature reporting the possibility of vertical transmission of coronaviruses from mother to infant during breastfeeding as of 17 April 2020 The infant in this study was never tested for SARS-CoV infection.
cord-346389-gbmnoo84	2020	
cord-346502-x2b0ao3q	2019	
cord-346777-zmmnn9b2	2019	title: Middle East respiratory coronavirus (MERS-CoV) spike (S) protein vesicular stomatitis virus pseudoparticle neutralization assays offer a reliable alternative to the conventional neutralization assay in human seroepidemiological studies The present work describes the generation and validation of S protein-bearing vesicular stomatitis virus (VSV) pseudotype particles (VSV-MERS-CoV-S) in which the VSV glycoprotein G gene has been replaced by the luciferase reporter gene, followed by the establishment of a pseudoparticle-based neutralization test to detect MERS-CoV neutralizing antibodies under BSL-2 conditions. These results demonstrate that the MERS-CoV-S protein pseudotyped VSV particle-based neutralization assay would serve as a safe, reliable and highly specific alternative method to detect MERS-CoV neutralizing antibodies to be used for future sero-epidemiological studies. A laboratory-confirmed SARS-CoV patient serum sample and a panel of human sera with confirmed high neutralizing antibody titres to human coronaviruses 229E, HKU1, OC43 and NL63 were used in this study to evaluate the VSV-MERS-CoV-S particle-based neutralization assay for potential cross-neutralization.
cord-346787-uo8k6qic	2020	3 The remdesivir dosing regimen being evaluated in clinical trials (200 mg IV on day 1, then 100 mg IV on days 2 through 5 or 10) was substantiated by in vitro data and bridging the PK with the rhesus monkey experience to humans. Prophylactic and therapeutic remdesivir treatment significantly reduced MERS-CoV-induced clinical signs, viral titers in respiratory specimens and the severity of lung lesions compared to control animals. 14 In the SARS-CoV-2 study, remdesivir was again initiated shortly before viral titers are expected to peak at 12 hours post-inoculation and a dosing regimen equivalent to the regimen being tested in human COVID-19 clinical trials was used (10 mg/kg load ~ 200 mg in humans, then 5 mg/kg daily ~ 100mg daily in humans x 6 days). In a summary of safety data reported by the FDA from the a remdesivir clinical trial comparing 5 and 10day treatment courses in patients with COVID-19, Grade 3 and 4 ALT and/or AST elevations occurred in 7% patients.
cord-347128-6lyoz8nn	2020	O-acetylated SAs interact with the lectin-like spike glycoprotein of SARS CoV-2 for the initial attachment of viruses to enter into the host cells. In RNA viruses, the S glycoprotein (PDB: 6VSB) is the biggest protein, heavily glycosylated and its N-terminal domain (NTD) sequence binds to the host receptor to enter the ER of host cells. However, MERS-CoV does not have a similar enzyme and thus MER-CoV binding to SA receptors is mediated by energetically reversible interactions of the lipid rafts with increased SA receptors [75] , thus enhancing dipeptidyl peptidase 4 (DPP4) or carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) recognition power and viral entry [76] and membrane-associated 78-kDa glucose-regulated protein (GRP78) [77] . Entry of host cells needs binding of S glycoproteins to the CEACAM receptor, forming S-protein-mediated membrane fusion. For example, impairment of ACE2 receptor glycosylation does not influence S-glycoprotein-ACE2 interaction, however, SARS-CoV-2 virus entry into respiratory epithelial host cells was downregulated [133] .
cord-347374-mryazbnq	2020	Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2–infected persons seroconverted by 2 weeks after disease onset. Using a well-characterized cohort of serum samples from PCR-confirmed SARS-CoV-2 and patients PCR-confirmed to be infected with seasonal coronaviruses and other respiratory pathogens, we validated and tested various antigens in different platforms developed in-house, as well as a commercial platform. We evaluated SARS-CoV-2-specific antibody responses in severe and mild cases by using serum samples collected at different times postonset of disease from 3 PCR-confirmed COVID-19 patients from France. We tested serum samples for SARS-CoV-2specific antibodies by using different ELISAs. After infection, all 3 patients seroconverted between days 13 and 21 after onset of disease (Figure 1) , and antibodies were elicited against the SARS-CoV-2 S, S1 subunit, and RBD, but only 2/3 patients had detectable antibodies to the N-terminal (S1 A ) domain.
cord-347460-9vechh4x	2020	Three components are crucial for SARS-CoV induced diseases: 1) the role of CD8+ T cells in defense against the virus, which causes apoptosis in the infected cells, 2) interactions of the virus with macrophages and dendritic cells, which initiate the early innate and subsequent adaptive immune responses, and 3) type I interferon (IFN) system, an innate response against viral infections, which can inhibit virus replication in the early phase. Existing information suggests that the SARS-CoV-infected airways and alveolar epithelial cells secrete abundant chemokines to attract immune cell infiltrations to the lungs, including macrophages and neutrophils, thereby causing damage due to high levels of proinflammatory cytokines and other mediators secreted by these cell types. After a decade of research on coronavirus, unfortunately, still there are no licensed vaccines, effective specific antivirals, nor drug combinations supported by high-level evidence to treat the infection, especially for newly emerging strains such as SARS-COV-2 [59] .
cord-347587-auook38y	2018	title: A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV In this study, we developed a novel neutralizing Nb (NbMS10) and its human-Fc-fused version (NbMS10-Fc), both of which target the MERS-CoV spike protein receptor-binding domain (RBD). Identification and characterization of MERS-CoV-RBD-specific Nbs. To construct the Nb (i.e., VHH) library, we immunized llama with recombinant MERS-CoV RBD (residues 377 to 588, EMC2012 strain) containing a C-terminal human IgG1 Fc tag (i.e., RBD-Fc) and isolated peripheral blood mononuclear cells (PBMCs) from the immunized llama. To examine of the role of the D539A mutation in DPP4 binding, we carried out an ELISA to detect the binding between DPP4 and The plates were coated with RBD-Fd protein (2 g/ml) and treated with or without DTT, followed by sequential incubation with serial dilutions of NbMS10 or NbMS10-Fc and goat anti-llama and HRP-conjugated anti-goat IgG antibodies.
cord-347889-lpd1olqq	2019	
cord-348278-is20odaq	2016	Middle East Respiratory Syndrome coronavirus (MERS-CoV) emerged in 2012 has since resulted in sporadic cases, intra-familial transmission and major outbreaks in healthcare settings. Middle eastern respiratory syndrome corona virus (MERS CoV): case reports from a tertiary care hospital in Saudi Arabia Epidemiological, demographic, and clinical characteristics of 47 cases of middle east respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Clinical aspects and outcomes of 70 patients with middle east respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia Middle east respiratory syndrome-coronavirus (MERS-CoV): a case-control study of hospitalized patients Dromedary camels and the transmission of middle east respiratory syndrome coronavirus (MERS-CoV) Middle east respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia Health-care associate transmission of middle east respiratory syndrome corona virus, MERS-CoV, in the Kingdom of Saudi Arabia
cord-348401-x2q9vyf2	2016	The MERS-CoV spike protein is a main determinant of virus entry into host cells as it mediates both binding to the DPP4 (dipeptidyl peptidase 4) receptor and fusion of the viral envelope with host cell membrane (Millet and Whittaker, 2014; Raj et al., 2013) . Immunofluorescence assay of MERS-CoV-infected Huh-7, MRC-5, and Vero-81 cells in presence of increasing concentrations of griffithsin. In all conditions, cells were infected with MERS-CoV strain EMC/2012 at an m.o.i. of 10, with griffithsin (1 mg/mL) added or not at different steps during virus entry. Because we have performed our assay using high m.o.i. and a short infection time, these results show the strong inhibitory activity of griffithsin on early steps of the MERS-CoV viral cycle. To better define which stage in the virus life cycle griffithsin acts on, we performed an infection assay using authentic MERS-CoV with griffithsin present at different times during viral entry steps (Fig. 4A) .
cord-348467-a2e3f161	2016	Most departing pilgrims (62%) were aware of a mod-erate to high infection risk from raw camel milk consumption, yet 21% of participants were willing to drink it. Nevertheless, among those who were aware of MERS-CoV, 27% did not fully realize the risk of catching the disease from unpasteurized camel milk, 15% were willing to drink raw camel milk, and 23% were keen to visit camel farm in Saudi Arabia (Table 3) . A unique finding to emerge from our study was that departing pilgrims with knowledge about MERS-CoV were significantly more aware of the risk of drinking raw camel milk (43% vs. Therefore, pilgrims who consume raw milk or other products are at risk of other zoonotic diseases if not MERS-CoV, and therefore, could benefit from appropriate health education.
cord-348821-2u6ki9dv	2020	The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. Thus, the purpose of this study is to perform a systematic review of epidemiological, clinical and laboratory characteristics of patients infected by COVID-19 or MERS-COV disease, and to compare COVID-19 and MERS-COV in the context of their incubation, laboratory features, admission rate of intensive cure unit (ICU) and rate of discharge and fatality, which will provide a comprehensive reference for clinical physicians in treatment of coronavirus diseases. https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 5 The study that met following criteria were included: (1) reporting clinical characteristics of COVID-19 or MERS-COV disease, (2) minimum sample size of five, (3) confirmed COVID-19 or MERS-COV disease, (4) English literature. Clinical predictors of mortality of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: A cohort study Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection
cord-349010-n4s8dzgp	2016	The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged as an important virus in 2012 and since then has caused multiple outbreaks in hospitals especially in the Kingdom of Saudi Arabia and outside the Arabian Peninsula [1] [2] [3] . Based on analysis of SARS data, interferon-ribavirin combination was suggested as a possible therapeutic option for the treatment of MERS-CoV infections [5] . Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study Inhibition of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by anti-CD26 monoclonal antibody Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol Towards the prophylactic and therapeutic use of human neutralizing monoclonal antibodies for Middle East respiratory syndrome coronavirus (MERS-CoV)
cord-349262-gnqbyc6t	2020	title: The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius) Dromedary camels remain the currently identified reservoir for the Middle East respiratory syndrome coronavirus (MERS-CoV). We tested nasal swabs, breath samples from animals within this herd by the real-time PCR. However, the nasal swabs are still the sample of choice in the diagnosis of MERS-CoV among the infected dromedary camel population. Detection of the virus in the air of positive camel''s herd [5, 6] may suggest the virus is excreted in the breath of the infected animals in high concentration. The aim of our study was to test the possibility of MERS-CoV shedding in the breath of the infected dromedary camels. Longitudinal study of Middle East respiratory syndrome coronavirus infection in dromedary camel herds in Saudi Arabia Dromedary camels and the transmission of Middle East respiratory syndrome coronavirus (MERS-CoV)
cord-349287-mwj2qby4	2015	The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Since asymptomatic zoonoses have been posited [72] , an absence of antibodies to MERS-CoV among some humans who have regular and close contact with camels may reflect the rarity of actively infected animals at butcheries, a limited transmission risk associated with slaughtering DCs [70] , a pre-existing cross-protective immune status or some other factor(s) resulting in a low risk of disease and concurrent seroconversion developing after exposure in this group. First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-tohuman transmission
cord-349300-x50tvq3a	2020	
cord-349643-jtx7ni9b	2016	Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. F rom September 2012 through April 27, 2016, a total of 1,728 laboratory-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infections, leading to 624 deaths (36% case-fatality proportion), had been reported to the World Health Organization (WHO) (1) . Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody protects rabbits from MERS-CoV infection
cord-349661-ppw80s0l	2017	
cord-349680-rz2ep5jf	2015	
cord-349781-l93978vq	2018	Little is known about the pathogenesis and innate antiviral response in primary human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) upon MERS-CoV infection. In this study, we assessed MERS-CoV replication as well as induction of inflammatory cytokines and chemokines in MDMs and immature and mature MDDCs. Immature MDDCs and MDMs were permissive for MERS-CoV infection, while mature MDDCs were not, with stimulation of proinflammatory cytokine and chemokine upregulation in MDMs, but not in MDDCs. To further evaluate the antiviral activity of well-defined drugs in primary antigen presenting cells (APCs), three compounds (chloroquine, chlorpromazine and toremifine), each with broad-spectrum antiviral activity in immortalized cell lines, were evaluated in MDMs and MDDCs to determine their antiviral effect on MERS-CoV infection. However, MERS-CoV continued to propagate in immature MDDCs up to 8 days pi, demonstrating differential infection and replication capabilities in MDMs and immature MDDCs. To compare the ability of MERS-CoV to induce innate immune responses in three types of APCs, the release of cytokines and chemokines was measured from virus-or mock-infected cells.
cord-349812-nw1nlc1y	2020	To examine the current status of non-pharmaceutical preventive behaviors practiced during the COVID-19 outbreak and factors affecting behavioral activities, we compared to the 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in Korea. 2,3,7,15-18 The current study aimed to quantify and compare the individuals'' adherence to social distancing and transmission-reducing behavioral practices during the COVID-19 and MERS-CoV outbreaks in Korea. Sex, age, occupation, self-reported household economic status, residential area, presidential job approval rating, party identification, and affective risk perception as participants'' characteristics, were investigated to identify factors influencing non-pharmaceutical preventive behaviors. 2,3,7,15-17,20-22 First, our study showed a marked increase in non-pharmaceutical preventive behaviors such as social distancing, wearing of face masks, and washing of hands, evenly, across all subgroups during COVID-19 compared to 2015 MERS-CoV. In conclusion, the present study suggests, for the first time, the level of the practice rate of non-pharmaceutical preventive behaviors and influencing factors during 2020 COVID-19 and 2015 MERS-CoV in Korea.
cord-349907-dwhyx97y	2017	Therefore, in this study, a duplex real-time reverse transcription (RT)-PCR method was developed based on primers and probes that target the conserved spike S2 region of SARS-CoV, SARS-like bat CoVs, MERS-CoV, and MERS-related bat CoVs. For the universal detection of SARS-CoV and SARS-like bat CoVs, consensus primers and probes (Fig. 1a) were designed based on the conserved sequences of the spike S2 region by aligning the following reference sequences: human SARS-CoVs Sino1 (GenBank no. The specificity of the real-time RT-PCR method developed in this study was evaluated using RNAs from several RNA viruses, including MERS-CoV (KOR/KNIH/ 002_05_2015), a recombinant plasmid for the bat CoV HKU4 strain, and RNA from a bat fecal sample containing SARS-like bat CoV. The new real-time RT-PCR method also showed positive results for RNA extracted from a fecal sample containing SARS-like bat CoV (B15-21) [7] .
cord-350733-0zghspb8	2020	
cord-350925-1h6pbfwp	2020	Transmission of viruses through air can happen via droplets or aerosols generated during coughing, sneezing, talking, singing or breathing (Jones and CoV-2 is that most studies performed only focused on the detection of viral RNA and do not correlate to the infectivity of these viral particles. Therefore, in this systematic review, the viability/stability of aerosols containing SARS-CoV and MERS-CoV viruses will be discussed to provide information on potential mitigation strategies for SARS-CoV-2 airborne transmission. The presence of MERS-CoV was also confirmed by RT-PCR of viral cultures of 4 out of 7 air samples from two hospitals in South Korea (Kim et al., 2016) , and showed to be very stable in aerosol at 20°C and 40% relative humidity (van Doremalen et al., 2013) .
cord-351186-llnlto7p	2015	Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments. Through personal and phone interviews we contacted employees at business facility in Saudi Arabia who may have had contact with Patient #1 during the incubation period; we investigated the places he visited, presence or absence of MERS symptoms in the individuals he contacted, history of visiting medical facilities in the Middle East, and history of consuming camel milk or meat, among other things.
cord-351413-3nfukrfl	2019	title: Spatiotemporal Clustering of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Incidence in Saudi Arabia, 2012–2019 We analyzed the spatiotemporal clustering of the MERS-CoV incidence in Saudi Arabia between 2012 and 2019 at the city level by using Kulldorff''s spatial scan statistics via SaTScan 9.6 [39] . The results of the spatiotemporal cluster analysis of MERS-CoV infection, using years and months as the time aggregates from 2012 to 2019, showed significant most likely and secondary clusters in Saudi Arabia (Table 3; Table 4 and Figure 5 ; Figure 6 ). Wadi The results of the spatiotemporal cluster analysis of MERS-CoV infection, using years and months as the time aggregates from 2012 to 2019, showed significant most likely and secondary clusters in Saudi Arabia (Table 3; Table 4 and Figure 5 ; Figure 6 ). Community case clusters of middle east respiratory syndrome Coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: A descriptive genomic study
cord-351685-n70tkf38	2020	
cord-351760-698voi9y	2018	The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. In vivo study demonstrated that prophylaxis with m336 reduced virus titers in the lung of rabbits infected with MERS-CoV [15] , and m336 also provided transgenic mice expressing human DPP4 with full prophylactic and therapeutic protection from MERS-CoV [16] . A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein Prophylaxis with a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection Passive Transfer of a Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV
cord-351852-ilxaurgt	2020	This study investigated the level of post-traumatic stress disorder (PTSD) and turnover intention, the relationship between PTSD and turnover intention, and the buffering effect of supervisor support among nurses post-MERS outbreak. We collected data pertaining to PTSD, turnover intention, supervisor support, work-related factors, and socio-demographic factors through a structured survey distributed to the nurses at the hospitals after the outbreak. To date, there is a lack of studies investigating the relationship between post-traumatic stress and turnover intention among nurses in the event of outbreak epidemics, such as MERS. The purpose of this study was to examine the levels of PTSD and intention to leave among a sample of Korean nurses who were directly involved in the care during the MERS outbreak, as well as the buffering effects of supervisor support on this relationship.
cord-352256-qxdakdk0	2020	
cord-352322-tsjwnvkk	2020	As consequences of such genomic mutation and recombination the transmissible gastroenteritis virus (TGEV) of swine and the bovine CoV (BCoV) likely originated from the closely related canine coronavirus (CCoV) (Pratelli, 2011) . Coronaviruses of farm animals including large and small ruminants, dromedaries, horses, pigs and chickens were reviewed; cetacean CoVs were also considered, as marine mammals are a food source in many countries around the world. Since the first case of human infected by the MERS-CoV was identified in September 2012 in Saudi Arabia (World Health Organization, 2019), interest to dromedaries as sources of the virus increased and the isolated strains were shown to be genetically very similar to those isolated from humans (Omrani, Al-Tawfiq, & Memish, 2015) . Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States Infection with a new porcine respiratory coronavirus in Denmark: Serologic differentiation from transmissible gastroenteritis virus using monoclonal antibodies
cord-352492-6ihyiwgb	2018	title: Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively STUDY DESIGN AND METHODS: PCs and plasma were spiked with high titers of cell culture–derived EBOV and MERS‐CoV, treated with various light doses of ultraviolet C (UVC; THERAFLEX UV‐Platelets) or methylene blue (MB) plus visible light (MB/light; THERAFLEX MB‐Plasma), and assessed for residual viral infectivity. The results of the infectivity assay demonstrated that UVC irradiation dose-dependently inactivated EBOV and MERS-CoV in plasma-reduced PCs (Table 1 ). Although EBOV is highly infectious and low doses of less than 10 plaque-forming units of the virus are sufficient to cause disease, 32 the ability of the UVC-and MB/ light-based systems to reduce MERS-CoV and EBOV infectivity in blood products by several log steps may be sufficient to eliminate or significantly reduce the risk of transmission via the transfusion of PCs or plasma.
cord-352527-eeyqh9nc	2019	A number of MERS vaccines have been developed based on viral RBD, including nanoparticles, virus-like particles (VLPs), and recombinant proteins, and their protective efficacy has been evaluated in animal models, including mice with adenovirus 5 (Ad5)-directed expression of human DPP4 (Ad5/hDPP4), hDPP4-transgenic (hDPP4-Tg) mice, and non-human primates (NHPs) [88] [89] [90] [91] [92] [93] [94] . Receptor usage of a novel bat lineage C Betacoronavirus reveals evolution of Middle East respiratory syndrome-related coronavirus spike proteins for human dipeptidyl peptidase 4 binding Recombinant receptor-binding domains of multiple Middle East respiratory syndrome coronaviruses (MERS-CoVs) induce cross-neutralizing antibodies against divergent human and camel MERS-CoVs and antibody escape mutants A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein A novel nanobody targeting Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain has potent cross-neutralizing activity and protective efficacy against MERS-CoV
cord-352741-0pdeehai	2020	In this report, we will review the published reports about the histopathologic findings of lung tissue in the patients infected with SARS-CoV-2 in comparison with 2 other coronaviruses that have caused outbreaks, ie, SARS-CoV-1 and MERS-CoV. The keywords for searching were "lung," " pulmonary," and CoVs, ie, "severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2])," "coronavirus disease (COVID-19)," "pathology," "biopsy," "autopsy," "histopathology," "severe acute respiratory syndrome (SARS)," and "Middle East Respiratory syndrome (MERS)." Histological examination of lung in rare cases reported from SARS-CoV-2 showed "edema, bilateral diffuse alveolar damage with cellular fibromyxoid exudates, desquamation of pneumocytes and hyaline membrane formation," indicating acute respiratory distress syndrome. 19 One histopathologic finding in the new SARS-CoV-2infected lung disease that has not been reported in the previous epidemics of coronaviruses is the presence of pulmonary fibrosis that can be indicative of future pulmonary dysfunction if the patient recovers. Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore
cord-352899-bt2xg0ha	2016	
cord-353121-ot7jsx20	2019	We evaluated the neutralizing activity in serum from three patients >1 year after recovery from Middle East respiratory syndrome (MERS) associated with mild pneumonia treated with antivirals during the MERS outbreak in South Korea at 2015. We evaluated the neutralizing activity in serum from three patients >1 year after recovery from Middle East respiratory syndrome (MERS) associated with mild pneumonia treated with antivirals during the MERS outbreak in South Korea at 2015. So, significant neutralizing activity was not demonstrated in any sera of three patients with mild pneumonia >1 year after being successfully treated with antiviral agents and recovering from MERS coronavirus infection. So, significant neutralizing activity was not demonstrated in any sera of three patients with mild pneumonia >1 year after being successfully treated with antiviral agents and recovering from MERS coronavirus infection. In conclusion, neutralizing activity was not demonstrated in any sera of three patients with mild pneumonia >1 year after being successfully treated with antiviral agents and recovering from MERS-CoV infection.
cord-353342-2n6kqyeo	2016	title: Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Quantitative data, such as viral loads and antibody titers, could enable comparisons with related diseases, in particular, severe acute respiratory syndrome (SARS), for which studies of natural history were conducted in the aftermath of the 2002-2003 epidemic [7] . DISCUSSION We studied quantitative viral excretion and serum antibody kinetics of a substantial group of hospitalized patients infected with MERS-CoV. Detection of SARS coronavirus in patients with severe acute respiratory syndrome by conventional and real-time quantitative reverse transcription-PCR assays
cord-353495-c3s5n5vo	2014	
cord-353704-lfndq85x	2020	In contrast, SARS-CoV, MERS-CoV and the newly-identified SARS-CoV-2 are highly pathogenic, causing severe lower respiratory tract infection in relatively more patients with a higher chance to develop acute respiratory distress syndrome (ARDS) and extrapulmonary manifestations. The 2019 novel HCoV (2019-nCoV), which has subsequently been renamed SARS-CoV-2, is the causative agent of the ongoing epidemic of coronavirus disease 2019 (COVID19) , which has claimed more than 3,120 lives and infected more than 91,000 people as of March 3, 2020 [19] . All these four communityacquired HCoVs have been well adapted to humans and are generally less likely to mutate to cause highly pathogenic diseases, though accidents did occur for unknown reasons as in the rare case of a more virulent subtype of HCoV-NL63, which has recently been reported to cause severe lower respiratory tract infection in China [38] . Alternatively, whereas bat alpha-CoVs serve as the gene pool of HCoV-229E, alpacas and dromedary camels might serve as intermediate hosts that transmit viruses to humans, exactly as in the case of MERS-CoV [69] .
cord-353732-7hjsux4m	2016	The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. Therefore, as part of a collaborative effort among colleagues from the Gulf States and Eastern Mediterranean and with the support of the World Health Organization and International Severe Acute Respiratory and Emerging Infection Consortium, we undertook a survey to assess feasibility of conducting a clinical trial of convalescent plasma therapy for patients with MERS-CoV infection in KSA. Our survey results indicate that the research infrastructure at many acute care facilities in Saudi Arabia is likely generally sufficient to conduct a RCT to investigate the efficacy of convalescent plasma treatment for severely ill patients with MERS-CoV.
cord-353965-0bb729sp	2016	There was a statistically significant positive correlation between mortality and old age (r =0.633), obesity (r =0.712), diabetes mellitus (r =0.685), renal failure (r =0.705), chronic heart diseases (0.591), COPD (r =0.523), malignancy (r =0.692), kidney transplantation (r =0.644) and liver cirrhosis (r =0.525) (P <0.05). Our study showed that most of the expired patients presented with bilateral pulmonary infiltrates or unilateral infiltrates, but most of the survivors presented with normal radiology or increased bronchovascular markings, and this difference in the results was statistically highly significant (P < 0.01) ( Table 2) . Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis associated with a poor outcome of ICU admitted MERS corona virus infected patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis associated with a poor outcome of ICU admitted MERS corona virus infected patients.
cord-354272-99vw735a	2017	title: Retrospective, epidemiological cluster analysis of the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic using open source data In an effort to better understand the patterns of transmission, a retrospective analysis of epidemiological clusters identified throughout the ongoing MERS-CoV epidemic was conducted using open-source data. Several key search terms were utilized to capture all cluster-related literature, including ''MERS-CoV'', ''nosocomial'', ''cluster'', ''transmission'', ''superspreader'', ''contact tracing'', and ''healthcare worker''. An exported cluster was defined as any cluster that resulted from verified travel of an index case (from an area of known MERS-CoV transmission) within one incubation period (14 days) of symptom onset. If a case was reported from the city during the estimated time in which there was ongoing nosocomial transmission, had no travel or camel exposure in the 14 days prior to illness onset, and had no known household contact with a confirmed MERS-CoV case, the case was included in the case count for that particular nosocomial cluster.
cord-354302-l2kywzro	2014	Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. T he Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 related to a fatal human case of pneumonia in Saudi Arabia (1) . MERS-CoV shedding started during 1-2 dpi, as detected by the presence of infectious virus and viral RNA by qPCR in nasal swab samples. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels
cord-354474-hbl2ywix	2020	As the Middle East respiratory syndrome coronavirus (MERS-CoV) continues to occur in small outbreaks in Saudi Arabia, we aimed to assess the knowledge, attitudes and intended practices of healthcare workers (HCWs) during the early stage of the COVID-19 pandemic and compare worry levels with previous findings during the MERS-CoV outbreak in 2015. To further understand the knowledge, attitudes and intended practices of HCWs during the early stage of the COVID-19 pandemic, it is particularly beneficial to obtain their input, especially in an area of the world where other respiratory viral illnesses are either endemic, such as MERS-CoV, or seasonal, such as influenza. The perceived adequacy of knowledge, hygienic practice changes and HCW attitudes toward infection control measures were assessed using a series of Likert-based questions (Supplementary Tables S2-S4 ). The level of knowledge of HCWs toward viral infection outbreaks during the current COVID-19 pandemic are much higher compared to the previous study conducted in the same institution during MERS-CoV a few years ago [15] .
cord-354536-c9v9kbw8	2020	This article introduced the origin, virological characteristics and epidemiological overview of SARS-CoV-2, reviewed the currently known drugs that may prevent and treat coronavirus, explained the characteristics of the new coronavirus and provided novel information for the prevention and treatment of COVID-19. 18 In view of the curative effect of ribavirin in the treatment of diseases caused by SARS-CoV and MERS-CoV, 21 it is expected to become one of the effective drugs to treat coronavirus. 16 The "Pneumonitis Diagnosis and Treatment Scheme for New Coronavirus Infection (Trial Version 7)" states that aerosolized interferon alpha can be used as a trial treatment against SARS-CoV-2 virus to improve the virus clearance effect of respiratory mucosa in patients. 64 It has been revealed that chlorpromazine is a broad-spectrum virus inhibitor that can inhibit HCV, alpha virus, and various coronaviruses including human coronavirus 229E, SARS-CoV and MERS-CoV in vitro.
cord-354582-fniymnmf	2020	In this review, we systematically describe the role of reverse genetics technology in studying the effects of coronavirus proteins on viral virulence and innate immunity, cell and tissue tropism and antiviral drug screening. Recently, reverse genetics techniques, including targeted RNA recombination, in vitro ligation and bacterial artificial chromosome systems, vaccinia virus vectors and transformation associated recombination (TAR) cloning, have been successfully used to manipulate the genome of coronaviruses (Fig. 2 ). Using a recombinant SARS-CoV strain with reduced nsp3 de-ADP-ribosylation activity showed that this mutant strain led to virus attenuation in mice but protected them from an otherwise lethal SARS-CoV infection and significantly enhanced the innate immune response, indicating that it is an important virulence factor for SARS-CoV . The N protein plays an important role in viral pathogenesis since BALB/c mice immunized with recombinant virus MVA-MERS-N exhibit stronger T cell responses and anti-N monoclonal antibodies protect mice from lethal infection by MHV (Nakanaga et al., 1986; Veit et al., 2018) .
cord-354738-4rxradwz	2014	In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. Various publications reviewed bats globally as carriers and potential reservoir hosts of human-pathogenic and zoonotic viruses [3] [4] [5] [6] [7] [8] [9] [10] , while hardly anything is known about human-pathogenicity of European bat viruses apart from lyssaviruses. Similar to the case of the LLOV filovirus, virus isolates and prevalence studies in both humans and bats could improve knowledge and clarify their zoonotic potential. Sero-prevalence studies should be conducted on the orthoreoviruses isolated from European bats, especially as a closely related virus was detected in a diseased child in Slovenia [83] . Other bat viruses detected by using molecular techniques should be isolated (e.g., MERS-like CoV or Bat Bunyavirus) to allow for characterization and follow-up sero-prevalence studies.
cord-355290-m8875kdy	2015	
cord-356007-6b0w36l9	2018	OBJECTIVE: To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications. Of these 10 available HCP, 9 reported prolonged, close contact with an unrecognized patient case before implementation of MERS-CoV IPC measures and with limited PPE use ( Table 3 ). Among the 10 interviewed HCP cases, the time from first positive MERS-CoV result to serum collection was 55-61 days, and 1 was seropositive: a 32-year-old female who had reported headache, muscle aches, and productive cough. Among them, 9 HCP (33%) tested rRT-PCR positive for MERS-CoV; 5 reported contact with index patient B before At hospital B, 34 of 50 MERS-CoV rRT-PCR-negative HCP contacts of cases (68%) were interviewed and provided serum. One was seropositive, a physician who had close, prolonged contact with index B after isolation and while wearing recommended PPE; however, he had previously tested rRT-PCR positive for MERS-CoV in 2013.
cord-356192-8b96rgqa	2017	title: Two deletion variants of Middle East respiratory syndrome coronavirus found in a patient with characteristic symptoms Significant sequence variation of Middle East respiratory syndrome coronavirus (MERS CoV) has never been detected since it was first reported in 2012. To predict the function of the E protein of MERS CoV, we aligned the E and ORF5-E protein sequences of MERS CoV with those of two other coronaviruses, SARS-CoV and China Rattus coronavirus HKU24, using MEGA software (version 6.0) [11] . The truncated E protein with a deletion of aa 1-30 lacks the N-terminus and a major part of the hydrophobic transmembrane domain in MERS CoV variant 1, which might directly impair virus packaging and replication [24] . Genomic sequencing and analysis of the first imported Middle East Respiratory Syndrome Coronavirus (MERS CoV) in China Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein
cord-356219-wl9htpp2	2015	Two of the earliest Middle East respiratory syndrome (MERS) cases were men who had visited the Doha central animal market and adjoining slaughterhouse in Qatar. Sequence analysis showed the circulation of at least five different virus strains at these premises, suggesting that this location is a driver of MERS-CoV circulation and a high-risk area for human exposure. D romedary camels are likely the primary source of Middle East respiratory syndrome virus (MERS-CoV) infection in humans, but further evidence is needed to support their role in zoonotic transmission. Analysis of an outbreak associated with a barn in Qatar found dromedaries and humans to be infected with nearly identical strains of MERS-CoV (3) and further support for camels as reservoir came from a study in Saudi Arabia (KSA) that found widespread circulation of different genetic variants of MERS-CoV in camels, with geographic clustering of human and camel MERS-CoV sequences (4) . Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia
cord-356364-ipi81ce3	2015	In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. The colorimetry-based peptide substrate, TSAVLQ-para-nitroanilide (TQ6-pNA) (purity 95-99% by HPLC; GL Biochem Ltd, Shanghai, China), was used to measure the proteolytic activity of MERS-CoV M pro and its mutants throughout the course of the study as described previously [25, 28] . In addition, although the K d values of wild-type SARS-CoV M pro without or with substrates show no significant difference (Table 2) , it was possible to detect substrate-induced dimerization at a protein concentration of 1 μM by AEC [33] . Biochemical and AUC studies indicated that MERS-CoV M pro shows almost the same proteolytic activity as SARS-CoV M pro ; although it is a monomer in aqueous buffer and displays substrate-induced dimerization (Fig 6) .