key: cord-0907831-zqkripoq
authors: Panigrahi, Gagan Kumar; Sahoo, Shraban Kumar; Sahoo, Annapurna; Behera, Shibasish; Sahu, Snigdharani; Dash, Archana; Satapathy, Kunja Bihari
title: Bioactive molecules from plants: a prospective approach to combat SARS-CoV-2
date: 2021-07-20
journal: ADV TRADIT MED (ADTM)
DOI: 10.1007/s13596-021-00599-y
sha: 4454e84eb7f0845746cbbee77009ccfe45dae986
doc_id: 907831
cord_uid: zqkripoq

ABSTRACT: The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or 2019 Novel Coronavirus (2019-nCoV) has put the entire globe into unrest, primarily due to unavailability of specific drug against the viral proteins. In the last two decades the world has withstood many contagious disease crashes. SARS-CoV-2 has put the world and the mankind in danger. It is spreading unstoppably all over the world. The virus is evolving and thus the pathogenicity of SARS-CoV-2 strains has been different and making it difficult to develop a broad-spectrum anti-viral molecule that would be effective against all the SARS-CoV-2 variants. This imperative situation demands development of molecules for effective treatment against SARS-CoV-2. The phytomolecules or the bioactive molecules of plants could be a great alternative to combat SARS-CoV-2. The bioactive molecules with their antiviral properties and the secondary metabolites may effectively deactivate the functioning of viral proteins. The structural configuration of 2019-nCoV proteins and genomic information are available, thus contributing immensely for fast molecular docking studies and hence, enables screening of numerous accessible phytomolecules. In the current study, we have essentially highlighted common phytomolecules against the known viral proteins and described the mode of action of few plant-derived molecules which have the potential to suppress the activity of the viral proteins. GRAPHIC ABSTRACT: [Image: see text]

The outburst situation caused due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represents a serious public health crisis across the globe. Since, December 2019, the whole world is suffering from the crisis of Corona virus. The virus is supposed to be originated from bats and latter on transmitted to humans. The outbreak of this human pathogen emerged in the city of Wuhan in China, and resulted to human disease, termed as COVID-19 (Arti and Bhatnagar 2020; Burki 2020; Chen et al. 2020; Huang et al. 2020) . World Health Organization (WHO) declared Public Health Emergency of International Concern (PHEIC) owing to its fast rate of transmission within the humans (Chan et al. 2020; Chen et al. 2020; Li et al. 2020a, b; Sun et al. 2020) . Over 14.57 million cases have been detected in 213 countries till now. The virus possesses crown like spikes on its outermost layer, so it was named as coronavirus (Fig. 1) . The SARS-CoV-2 belongs to the beta (β), Coronavirus genus, closely related to the previously identified severe acute respiratory syndrome Coronavirus (SARS-CoV), family Coronaviridae, order Nidovirales and the sub family Orthocoronaviridae Shereen et al. 2020; Wu et al. 2020; Zhou et al. 2020) . Middle East Respiratory Syndrome (MERS) and severe acute respiratory syndrome (SARS) are commonly caused by viruses belonging to the Coronaviridae. Coronaviridae has two sub families; Torovirinae and Coronavirinae and the members of Coronaviridae family affects the mammals and aves . The virus is 65-125 nm in diameter and the genomic content is estimated to be 26-32 kilobases. SARS-CoV-2 is an RNA virus and it contains single-stranded RNA genome. The virus has four subgroups i.e. Alpha (α), Beta (β), Gamma (γ) and Delta (δ). The Alpha (α) and Beta (β) corona virus infect mammals. The Beta (β) corona virus causes respiratory illnesses to humans and the Gamma (γ) and Delta (δ) corona virus affect aves and some selective mammals (Woo et al. 2012) . SARS-CoV-2 makes use of its own proteins to safely harbour in the host cells (Fig. 1) . Reportedly, a densely glycosylated spike (S) protein, SARS-CoV-2 main protease (M pro ) and RNA-dependent RNA polymerase (RdRp) are defining features paving the path of virus from entry to infection in the host cell (Cui et al. 2019; Lung et al. 2020; Ton et al. 2020; Wrapp et al. 2020) . Essentially, the S protein undergoes extensive structural reorganization in order to fuse with the host membranes, thus establishing a physical link between the virus and the host cell (Booth et al. 2003; Li et al. 2020a ). Eventually, a stable conformation is established (Wrapp et al. 2020) . RdRp catalyzes the replication event, resulting in the synthesis of viral RNA. Remarkably, SARS-CoV and SARS-CoV-2 share similar nucleotide sequences and resulting RNA-dependent RNA polymerase . The SARS-CoV-2 proteins, metabolites and host cell factors can be targeted to reduce the viral replications within the host cells as for instance; the viral protein M pro facilitates the synthesis of functional viral proteins out of the precursors (Fig. 2 ). M pro , S and RdRp proteins can be targeted for developing diagnostics, antibodies and vaccines. Human corona virus (HCoV), HCoV OC43, MERS-CoV and SARS-CoV are some of the viruses which causes respiratory problems in human and are being transmitted from one individual to another. This viral infection is transmitted from human to human through the coughed, sneezed droplets or by the contact of infected surface. The solved three dimensional structures of the viral proteins provide an outstanding ground for discovering specific ligands . In South-east countries like South Korea, China, Japan and India, many traditional medications are used to treat SARS-CoV-2, but the efficiency of the compounds are limiting and molecular mechanisms are also unclear. Plants possess amazing defense competence towards diseases ). The phytomolecules are also known as the bioactive compounds which have the tendency to modify the cellular physiological processes. Here, we highlight several phytomolecules having the ability to restrict the activity of SARS-CoV-2 and thus future studies may reveal the underlying molecular mechanism(s) and the efficacy of these phytomolecules.

People are worstly affected by Covid-19 in different ways. The most common symptoms of Covid-19 include fever, dry cough, and tiredness. It also shows symptoms like diarrhoea, headache, loss of taste or smell, aches and pain, rash on skin, discoloration of finger on toes etc. Wang et al. 2020a,b,c) . Transmission of SARS-CoV-2 is severe as compared to the SARS-CoV. Severe lung damage pneumonia like symptoms were seen in patient suffering from SARS-CoV-2 . The Chinese center for disease control and prevention sent a medical emergency team to assist the health authorities of Hubai province and Wuhan city to inspect about the disease, but later WHO gave confirmation about the outbreak of the disease. According to WHO the disease was not caused by any particular animal in Hunan South China sea food market place. Subsequently the transmission of the disease occurred rapidly, the situation became out of control when the whole world was affected badly. The genomic evidences related to SARS-CoV-2 were published (Ferh et al. 2017; Zheng 2020) . All possible ways including vaccines, monoclonal antibodies, oligo nucleotides, interferons and small molecules, drugs were tried to be developed for the control of SARS-CoV-2. WHO recommended to practise social distancing among people so as to deaccelerate the higher rate of infections.

In countries including China, United States of America, Italy, India and many other countries, SARS CoV-2 had spread rapidly (Giovanetti et al. 2020; Paraskevis et al. 2020) . Several studies suggested that bat may be the cause of SARS-CoV-19, but it is not confirmed that bat is the stockpile of SARS-CoV-2. CoVs acts as nonfatal pathogen, which cause only common cold in case of humans (Li et al. 2005a,b; Hampton 2005; Banerjee et al. 2019; Giovanetti et al. 2020; Paraskevis et al 2020; Paules et al. 2020 ).

Covid-19 mainly spreads and enters into human body in 3 different ways; firstly by droplets transmission-by sneezing, coughing; secondly by the patient it transmits through contact-by touching mouth, nose and eyes in contaminated area; thirdly, by aerosol transmission (Guan et al. 2020; Jin et al. 2020) . In case of humans, symptoms such as abdominal discomfort and diarrhoea are also prominent. It was found that the Angiotensin-Converting Enzyme 2 gene (ACE2) was highly expressed in Covid-19 patients (Zhang et al. 2020a, b) . The most general symptoms of this disease are cold, fever, myalgia or fatigue, common pneumonia and complicated dyspnoea and less common symptoms are headache, diarrhoea, hemoptysis, runny nose and phlegm producing cough. The affected individuals showing mild symptoms usually get recovered within one week whereas individuals showing acute symptoms are prone to damage in alveolar tissues and subsequently leading towards severe respiratory failure. Mainly the old aged patients already suffering from diseases such as cirrhosis, tumour, hypertension, diabetes and coronary heart damage get very severe problems and proven to be highly fatal (Arti et al. 2020; Huang et al. 2020; Li and Clercq 2020; Li et al. 2020a, b) . As compared to other countries, the proportion of infection in India was low i.e. 1.9%. In India lockdown started from 25th March 2020, all over the country, after the rapid transmission of Covid-19 and situation was back to normal around the start of 2021. But, unusually India is witnessing the dreadful nature of this pandemic now, where it is believed to be because of a variant strain of SARS-CoV-2. Currently, nation-wide crisis Fig. 2 Possible potential targets to restrict the activity of SARS-CoV-2. There are number of promising targets which can be exploited to inhibit the viral infection. Metabolites including nucleoside analogues and antimetabolites can be targeted to prevent viral replication. Likewise, host cell proteins such as ACE-2 (Angiotensin Converting Enzyme-2), Importin α1-β1 inhibitors and Signal transducers and activators of transcription 1 (STAT1) can also be targeted. Three categories of proteins; structural, non-structural and accessory can also be targeted to repress the activity of the virus

(29)

• Nucleoside analogoues

Accessory (9) 3a, 3b, 6, 7a, 7b, 8, 9b, 9c, has again led to lockdown situations and speculations suggest that the rise in Covid infections would reach around the mid of May, 2021.

On December 2019, an unknown outburst of viral Pneumonia in Wuhan city made clinicians across the globe to analyze different therapeutics to defy Covid-19. Since definite vaccine for Covid-19 was not discovered, the disease got escalated all over the world and forced the clinicians to use former convenient drugs for the treatment.

Covid-19 treatment may involve targeting of Autophagy and endocytic signaling events ). Primarily, virus and host cell interaction is critical and there are several check-points were suitable drugs may be targeted (Figs. 3 and 4). Essentially, SARS-CoV-2 mainly affected the lungs and majority of fatality was due to the collapse of respiratory system. Consequently, patients were first aided with oxygen therapy, extra corporeal membrane oxygenation (ECMO) and invasive mechanical ventilation. Many drugs such as remdesivir, ribavirin, nitazoxanide, penciclovir, chloroquine, nafamostat and favipiravir were tested in counter to this lethal disease on Vero E6 cells and was monitored that chloroquine and remdesivir were the most suitable drugs with less cytotoxic effects (Wang et al. 2020a, b, c) . In addition to these drugs, antibiotics such as hydroxychloroquine and azithromycin were able to control the viral growth. Lopinavir, baricitinb, interferon-α and ribavirin may be given to the patients with acute respiratory system, but addition of lopinavir has side effects like diarrhoea, nausea or liver damage (Hirsch et al. 2013) . Use of steroids can check the inflammatory damage, but a heavy dose has several harmful effects (Booth et al. 2003; Griffith et al. 2005; Minneci et al. 2009; Clark and Baillie 2020) . Plasma therapy was also under observation for the treatment of Covid-19. This therapy essentially involved in deriving antibodies from B-lymphocytes of the recovered patients. It can help in reducing inflammation and viral growth. Traditional Chinese Medicine (TCM) therapy was another choice for the treatment of Covid-19 as it was a successful therapy curing disease from ancient time. It was highlighted that Lian Hua Qing Wen and Shu Feng Jie Du capsules gave positive response in treatment of SARS-CoV-2 (Lu 2020). The western medicines and combination of western and traditional Chinese medicines were experimented separately for the effectiveness towards the disease and was found that the combination of western and traditional Chinese medicine was more effective. The combined medicine stabilized the body temperature in less time and also lowered the mortality rate. Vaccination was necessary to cease the transmission and develop immunity against Covid-19. Recombinant protein subunits for MERS, DNA plasmids, viral vectors, virus like particles and nanoparticles were used to develop the first vaccine.

The mRNA vaccine was first tested in humans on March 16, 2020 in United States of America. The vaccine mimics mRNA 1273 which encodes spike protein of SARS-CoV-2 and is primarily enclosed within nanomaterials. However, the understanding of the SARS-CoV-2-host interaction(s) and the underlying molecular mechanism(s) still remains blurred. 

The primary and secondary metabolites have different group of compounds (Fig. 5 ). Improvised analytical techniques would modulate in generating informations regarding bioactive molecules derived from various natural sources including plants. Thus, sophisticated analytical techniques and choosing right natural source may help in overcoming many diseases, particularly for those having no specific treatment. The major compounds that are categorized as primary metabolites and found in all the living systems include proteins, lipids, carbohydrates, nucleic acid and chlorophyll (Fig. 5) . Likewise, secondary metabolites include flavonoids, phenol acid, alkaloids, volatile oils, terpenes, saponins, tannins, and many more (Dias et al. 2012; Azmir et al. 2013; Woolley 2001; Panda et al. 2020) . Different species of plants accumulate specific secondary metabolites and also plays an imperative role during survival and adaptability process of the plant primarily by modulating the cellular homeostasis (Panigrahi and Satapathy 2020a, b, c; Sahoo and Satapathy 2020).

The modern science is exploring new natural derivatives present in variety of living organisms and subsequently these natural products display highly efficient therapeutic properties for treating various diseases (Dash et al. 2020 ). These natural products have diverse application and unique properties which are useful for medicine production processes (Kang et al. 2013 ). From ancient time, the traditional natural medicines are playing vital role in disease control and ancient medicine practitioners were expert in this field with or without knowledge of bioactive molecules. Now-adays researchers are focusing more on plant-baed bioactive molecules to overcome dreadful disease as these products have negligible side effects on humans (Kang et al. 2013) . The therapeutic capacity of medicinal plants is due to their chemical composition which primarily comprises of vitamins, minerals and bioactive molecules (Singh et al. 2020a ).

Many scientific studies suggest that the synthetic vitamins and minerals cannot give the benefits as much as natural products. The medicinal plants contain many minerals and vitamins that easily get assimilated by human body. Natural products contain more bioactive molecules as it has complementary action between vitamins, enzymes and (Singh et al. 2020b) . Synthetic drugs posses more side effects and have more disadvantages towards human body as compared to natural medicines (Singh et al. 2020b ). The plant products have phytomolecules containing active ingredients with therapeutic properties (Dias et al. 2012 ). The secondary metabolites are specific from species to species. Bioactive molecules harbour therapeutic, toxicological and immune stimulation properties and could prove to be an effective alternative against viral diseases (Panigrahi and Satapathy 2020d; Sahoo and Satapathy 2020). Across the globe, the mankind is facing the deadly effect of Covid-19. Every vaccine is under the trial basis and it has been reported that the drugs that were generally used for the Human Immunodeficiency Virus (HIV) such as lopinavir/ritovir can be used for treating Covid-19 patients (Wang et al. 2020a, b, c) . Some other drugs like pitavastatin, nelfinavir, perampanel and praziquantel can also be used against covid-19 . Plants are repositories of several types of natural bioactive molecules which might play a critical role in addressing the current pandemic. Essentially the various secondary metabolites which are secreted by the plant cells can be utilized for developing anti-viral drugs using plant biotechnological approaches (Fig. 6) . Usually secondary metabolites such as flavonoids, alkanoids, terpenoids and polyphenols possess antiviral properties (Yang et al. 2018; Khaerunnisa et al. 2020; Singh et al. 2020c ). Medicinal plants are abundantly rich in phenolic metabolites (Yang et al. 2018) . Molecular docking studies revealed that medicinal plants-derived phytomolecules such as quercetin, curcumin, kaempferol, catechin, naringenin, buteolin-7-glucoside, apigenin-7-glucoside, demethox-yeurcumin, obeouropein and epigallao-catechin that have the potential for combating against SARS-CoV-2 (Singh et al. 2020c ). These bioactive molecules display similar pharmacophore properties as nelfinavir as revealed in in silico analysis. The bioactive phytomolecules released from a range of plant species bears therapeutic properties against SARS-CoV-2.

prop-2-en-1-one, beta′-(4-Methoxy-1,3-phenylene)bis(2′hydroxy-4′,6′dimethoxyacrylophenone) and apiin are also effective anti-virals (Adem et al. 2020; Singh et al. 2020c ; Table 1 ). Lupane-type triterpenes, R-cadinol, labdane-type and abietane-type diterpenes, lignoids, curcumin and sesquiterpenes are few other identified bioactive compounds which would also play an vital role in defending the host cells against SARS-CoV-2 (Wen et al. 2007; Yang et al. 2020; Gong et al. 2008; Nguyen et al. 2012 ). In the last decade, many numbers of traditional Chinese herbs have been identified which were effective against SARS-CoV . Herbal extracts from Houttuynia cordata, Chinese Rhubarb extracts and beta-sistosterol from roots of Isatis indigotia that have the potential to impede the enzymatic activity of SARS-CoV Singh et al. 2020c ). Many more phytomolecules like epigallocatechin 

Viral diseases are causing a distressing threat for human beings across the globe. A number of viral diseases are continuously reported which predominantly display severe health related issues and unfortunately unavailability of effective antiviral cure makes these diseases more severe (Kapoor et al. 2017 ). Essentially, flaviviruses and alphaviruses are the causative agents for several types of viral diseases such as chikungunya, influenza and HIV which are still considered as potential threats. Similarly, the COVID-19 which resulted in a pandemic situation has badly affected a large number of population across the globe. As the rate of genomic mutation is faster in case of coronavirus, it has become difficult to develop effective synthetic drug-based treatment strategies (Irwin et al. 2016) . One of the drawbacks of synthetic antiviral drugs is that they display adverse side effects which would affect the human well-being. On the contrary, plant-derived drugs can be considered as a suitable alternative since herbal treatments exhibit minimal side effects with maximal health benefits (Biswas et al. 2019) . For several emerging viral diseases, plant-derived compounds exhibiting antiviral properties have been evaluated and found to be effective and most importantly have been propsed to be applied along with the pre-existing therapies so as to enhance the efficacy (Kapoor et al. 2017; Lillehoj et al. 2018) . The antiviral properties of the plant-based compounds are governed by a variety of mechanisms. It has been reported that few phytochemicals have the potential to restrict the entry of viruses primarily by ensuring unavailability of specific sites for attachment of viruses to specific host cells as the phytochemicals can bind to the carbohydrate moiety of the target host cell (Idris et al. 2016) . Also, few phytomolecules inhibit viral replication and propagation and thus prevents the infectious action of viruses (Kapoor et al. 2017) . Phytomolecules can be strategically employed against viral infection by targeting any possible viral replication check-points. For example, the phytochemical; epigallocatechin gallate (EGCG) specifically inactivates the viral as well as host enzymes (reverse transcriptase, protease, RNA polymerase) and ultimately restricts the viral growth (Lipson et al. 2017) . Another way the flavonoids restrict the viral RNA synthesis is by preventing protein phosphorylation resulting in inhibition of several viruses such as herpes simplex virus, influenza virus and HIV (Kumar and Pandey 2013) . Several phytochemicals including fiestin, baicalein and quercetagetin have the potential to inhibit the chikungunya virus essentially by restricting the viral replication events (Lani et al. 2016) . Similarly luteolin also possess antiviral replication activity during the post entry process as this phytochemical cannot inhibit the viral replication Fig. 6 Developmental routes for plant-based diagnostics and therapeutics against SARS-CoV-2. Plant-based secondary metabolites can be substantially utilized for developing anti-viral drugs using plant biotechnological approaches during the entry of virus into the host cell (Fan et al. 2016) . It is also evident from recent studies that the pinocembrin specifically inhibits Zika virus replication during late early stages (Lee et al. 2019) . Also, genistein effectively inhibits the post-replication events mediated by the entry of herpes B virus (Lee et al. 2019) . Interstingly, combinatorial effect of genistein and synthetic drugs such as ganciclovir and acyclovir has been found to be more effective (LeCher et al. 2019) . Similarly, around 43 alkaloids have been reported which are effective against influenza virus. Majorly, the alkaloids are believed to induce interferons and macrophages which enhances the immunogenic response against the virus (Moradi et al. 2018) . Likewise, alkaloids also play an important role in diminishing the effect of influenza virus by inhibiting the viral replication or by preventing the synthesis of viral proteins (Moradi et al. 2018) . Commelina communis contains homonojirimycin (HNJ), an alkaloid which strongly inhibits the infectious activity of influenza virus (Zhang et al. 2013) . Alkaloid such as loliolide extracted from Phyllanthus urinaria impairs the entry of Hepatitis C virus (HCV) into the host cell (Chung et al. 2016) . Also plant extract from Aglaia sp. possess antiviral activity owing to the presence of terpenes which can act against HIV-1 primarily by restricting the viral proliferation because of phytochemical-generated cytotoxic environment. In similar fashion, the transition phase between S and G2/M of the cell cycle is inhibited by the 3, 4-secodammarane triterpenoid, which ultimately prohibits the viral dissemination (Esimone et al. 2010) . Marrubium vulgare contains terpenes which are effective against HSV-1 (Fayyad et al. 2014 ). Honokiol, one of the lignin extracted from Magnolia tree are mostly used in Chinese medications (Fang et al. 2015) . Honokiol is effective against dengue virus as it can stall the synthesis of dsRNA and replication event. Similarly, 3-hydroxy caruilignan C (3-HCL-C), a lignin prevents the viral transcriptional and translational phases . One of the Coumarin (C4) is known to supress the IHNV infection, essentially by promoting cellular damage and preventing apoptosis and thus can be one of the potential alternative measures for generating anti-IHNV drug/vaccine (Hu et al. 2019) . A detailed study on the underlying molecular mechanism(s) which mediates silencing of viral activities inside the host cell is yet to be fully revealed.

Traditional plants have been widely explored for the treatment of various illness including viral infections. The major advantage of phytochemicals is that they exhibit minimal toxicity and side effects. Now-a-days researchers are keen to reveal more plant-based molecules having tremendous Yi et al. (2004) potential against various diseases. Thousands of plantderived secondary metabolites have been used as antiviral, antioxidant and antibacterial chemicals as revealed in several in silico and in vitro studies. Interestingly, phytochemicals along with other synthetic compounds including drugs can also be treated as an effective approach against viral infections. But, at the same time detailed molecular mechanism including the dosage potency of phytochemicals also need to be elucidated. Since most of the prevailing therapies against viral infections are synthetic drug-based which display adverse side effects, it is most important to approach for developing strategies which would be cost effective and less harmful for the human beings. In this context, phytochemicals can be considered as a suitable alternative.

The year 2020 and till now it has been a disastrous year for the world population due to sudden outbreak of Covid-19. Though the vaccines are given to the patients, but the recovery and disease infection rate is still at the peak, so the new drugs or vaccines with high efficiency is yet to be discovered. WHO strongly advocates in maintaining several preventive measures such as washing hands frequently, maintaining social distance, by avoiding crowded places and wearing mask frequently. Different lockdown plans are made by the government authorities to protect the public from this pandemic. Plant-derived bioactive molecules may play a significant role in developing traditional medications which would be a boon for the entire mankind. Many plants contain the natural derivative compounds having the antiviral properties, consequently effective drugs can be formulated and would be a stepping stone for combating against new strains of virus (Fig. 7) . Phytomolecules have tremendous potential to act as anti-viral or anti-pathogen agents. Now-a-days, Fig. 7 Strategy to restrict the synthesis of SARS-CoV-2 proteins inside the host cell. Plant-derived molecules can be effectively recruited in the host cell specifically to prevent viral proliferation the brutal spread of the coronavirus is a wham to the mankind. Combined application of phytomolecules and FDAapproved synthetic drugs can be proved to be highly effective and thus related studies could be beneficial for a long-term preventive measure against viral pathogens. Additionally, repurposing of known phytochemicals which are effective against virus can be practised. Furthermore, nanotechnological interventions such as encapsulation of antiviral phytochemicals in nanoparticles can enhance the stability and delivery within the host cells. In addition, exploring biodiversity rich regions can also be advantageous in isolating antiviral phytomolecules. It is absolutely important to explore the bioactive molecules-based therapeutic measures and get ourselves prepared for future encounter with virus.

Acknowledgements Authors thank the administration and management of Centurion University of Technology and Management, Odisha, India for their heartfelt support. We apologize to all colleagues whose work could not be discussed owing to space limitations. 

Ethical statement This article does not contain any studies involving animals performed by any of the authors. This article does not contain any studies involving human participants performed by any of the authors.

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Homonojirimycin, an alkaloid from dayflower inhibits the growth of influenza a virus in vitro

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes

SARS-CoV-2: an emerging coronavirus that causes a global threat

Isolated perfused lung extraction and HPLC-ESI-MSn analysis for predicting bioactive components of Saposhnikoviae Radix

A pneumonia outbreak associated with a new coronavirus of probable bat origin

A novel coronavirus from patients with pneumonia in China

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