key: cord-0967520-z8hy4oxj authors: Li, Tianbao; Huang, Tao; Guo, Cheng; Wang, Ailan; Shi, Xiaoli; Mo, Xiaofei; Lu, Qingqing; Sun, Jing; Hui, Tingting; Tian, Geng; Wang, Leyi; Yang, Jialiang title: Genomic Variation, Origin Tracing and Vaccine Development of SARS-CoV-2: A Systematic Review date: 2021-05-11 journal: Innovation (N Y) DOI: 10.1016/j.xinn.2021.100116 sha: b87ff9b7b3195e10a2a89d01aaa91dfe3ebe8abd doc_id: 967520 cord_uid: z8hy4oxj COVID-19 has spread globally to over 200 countries with more than 40 million confirmed cases and one million deaths as of November 1, 2020. The SARS-CoV-2 virus, leading to COVID-19, shows extremely high rates of infectivity and replication, and can result in pneumonia, acute respiratory distress, or even mortality. SARS-CoV-2 has been found to be continue rapidly evolving, with several genomic variants emerging in different regions throughout the world. In addition, despite intensive study of the spike protein, its origin and molecular mechanisms in mediating host invasion are still only partially resolved. Finally, the repertoire of drugs for COVID-19 treatment is still limited, with several candidates still under clinical trial and no effective therapeutic yet reported. Although vaccines based on either DNA/mRNA or protein have been deployed, their efficacy against emerging variants requires ongoing study, with multivalent vaccines supplanting the first generation vaccines due to their low efficacy against new strains. Here, we provide a systematic review of studies on the epidemiology, immunological pathogenesis, molecular mechanisms and structural biology, as well as approaches for drug or vaccine development for SARS-CoV-2. Coronaviruses have also been identified in several other mammalian hosts such as avian, bats, civets, and mice, among other species 13, 14 . Similarly, SARS-CoV-2 has raised major concerns globally, with clinical features ranging from mild or moderate upper-respiratory symptoms to severe cases involving respiratory, gastrointestinal, hepatic, renal, and neurological system failure [15] [16] [17] . In the worst case scenarios, SARS-CoV-2 infects lower respiratory tract, and can quickly develop into acute respiratory distress syndrome (ARDS), which requires mechanical oxygen support. The basic reproductive rate (R 0 ) is an epidemiological metric to estimate the extent of epidemic transmission without control measures, as well as to evaluate the efficiency of reducing the transmission of disease by human intervention. Initial evaluation of trends of COVID-19 transmission showed that R 0 is close to 2.5, which appeared similar to the spread of SARS-CoV in 2003, which had an R 0 of 2.90 (range: 2.3-3.7). However, the basic reproduction number of SARS-CoV-2 dropped markedly to lower than 1 after implementing strict physical distancing and preventive hygiene measures [18] [19] [20] . Globally, the R 0 of SARS-CoV-2 ranges between 2.5-7.1 when the absence of human intervention ( Figure 1A ). To date, no effective methods have been found that can prevent the spread of the epidemic, apart from emphasizing the need for extended social distancing, J o u r n a l P r e -p r o o f molecular/antibody testing for infections, and contact tracing to identify and isolate infected patients 5,21 . In addition, antibody testing can be applied to identify individuals with previous SARS-CoV-2 infection and those former patients with sufficient convalescent plasma may opt to donate blood to benefit the therapy of current patients. At the community level, antibody surveillance programs can be implemented to locally monitor public serological data in order to better inform public health policy, while increased molecular testing can be used to evaluate the efficacy of vaccination efforts 22,23 . Given these current strategies for epidemic control, development of affordable and accurate non-invasive nucleic acid and antibody tests is therefore urgently needed by community health services. In this study, we conducted a systematic review focusing on genomic variation, origin tracking, epidemiological characteristics, transmission mode, differences between virus strains, as well as pathological mechanisms, potential treatments, and recent advances in vaccine development. COVID-19 was declared to be a "pandemic" by the WHO on March 11, 2020, and more than 40 million cases were confirmed and one million deaths recorded across more than 200 SARS-CoV-2 is a beta-coronavirus that belongs to the same family as the highly The spike (S) glycoprotein was reported as a key factor in facilitating SARS-CoV-2 to enter host cells (Figure 3 ). The S protein, a component of the membrane comprised of the S1 and S2 subunits, gives coronaviruses their characteristic 'crown' appearance. The receptorbinding domain (RBD) and amino-terminal domain are found in the S1 subunit, while the S2 subunit contains the fusion peptide and heptad repeat regions, responsible for membrane fusion between virus and host cells 68,69 . Furthermore, a furan cleavage site for TMPRSS2 was reported at the boundary between S1 and S2, resulting in S protein cleavage during the progression of viral infection. This TMPRSS2 proteolytic cleavage site can also be used to distinguish SARS-CoV-2 from SARS-CoV. In addition, the SARS-CoV-2 RBD has a relatively higher binding affinity than that of SARS-CoV, which can at least partially explain why SARS-CoV-2 is highly contagious and exhibits increased infectivity 70 to examination can also confound diagnosis. In most countries, an increasing trend in confirmed cases during the early stages of the outbreak is followed by an exponential growth trajectory before the epidemic peaks. It is therefore difficult to compare the rates of infection and fatality between countries due to differences in the stages of outbreak, highly variable scopes of population testing, differences in the burden on their respective health care systems as well as general health status of the population, and differences in average population demographics 106 . Moreover, the elderly and people with underlying chronic disease are more susceptible to infection by SARS-CoV-2 at the beginning of the outbreak. The most common symptoms of early infection include mild fever, dry cough, and fatigue, while nasal congestion, diarrhea, and sore throat are rarely reported. However, some people close to COVID-19 patients, or in family cluster cases, initially showed no fever or respiratory symptoms but exhibited non-respiratory or cardiac-associated symptoms, such as The first confirmed case in North America was identified in USA. The first confirmed case in Europe was found in France. Mutant strains were found in South Africa, Britain and other countries. Pfizer and biontech's vaccine (BNT162b2) was approved by FDA for emergency use. Vaccine of Moderna (mRNA-1273) was approved by FDA for emergency use. Vaccine of Sinopharm was first approved in china. COVID-19 vaccine based on adenovirus developed in China was approved for use. Comprehensive Genome Analysis of 6,000 USA SARS-CoV-2 Isolates Reveals Haplotype Signatures and Localized Transmission Patterns by State and by Country Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions Predicting susceptibility to SARS-CoV-2 infection based on structural differences in ACE2 across species Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Melatonin is significantly associated with survival of intubated COVID-19 patients A comparative analysis of remdesivir and other repurposed antivirals against SARS-CoV-2 Integrative analysis reveals functional and regulatory roles of H3K79me2 in mediating alternative splicing An improved multivariate model that distinguishes COVID-19 from seasonal flu and other respiratory diseases Human Lung Tissue of Smokers, COPD, and IPF: Associations With SARS-CoV-2 COVID-19 ACE2-TMPRSS2-Furin-DPP4 Axis Obesity alters Ace2 and Tmprss2 expression in lung, trachea, and esophagus in a sex-dependent manner: Implications for COVID-19 Use of Continuous Glucose Monitoring to Assess TPN-induced Hyperglycemia in an Adult Patient with Severe COVID-19 Functional genomic screens identify human host factors for SARS-CoV-2 and common cold coronaviruses Host Immune Response Driving SARS-CoV-2 Evolution Structure and Drug Binding of the SARS-CoV-2 Envelope Protein in Phospholipid Bilayers Overexpression of the SARS-CoV-2 receptor ACE2 is induced by cigarette smoke in bronchial and alveolar epithelia Reply to 'SARS-CoV-2-associated critical ill myopathy or pure toxic myopathy?' SARS-CoV-2-associated critical ill myopathy or pure toxic myopathy? Coronavirus-19 Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Immunocompromised myasthenia gravis patient not infected with SARS-CoV-2 after close exposure -what is the risk of COVID-19? The eIF2alpha Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4 SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism Transcription factor-associated combinatorial epigenetic pattern reveals higher transcriptional activity of TCF7L2-regulated intragenic enhancers Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 LUBAC Suppresses IL-21-Induced Apoptosis in CD40-Activated Murine B Cells and Promotes Germinal Center B Cell Survival and the T-Dependent Antibody Response Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 Estrogen receptor beta signaling in CD8(+) T cells boosts T cell receptor activation and antitumor immunity through a phosphotyrosine switch COVID-19 Vaccine Development to Vaccination BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting Covid-19: UK approves Moderna vaccine to be given as two doses 28 days apart COVID-19 Vaccines: Current Status and Implication for Use in Indonesia Increased expression of TRIP13 drives the tumorigenesis of bladder cancer in association with the EGFR signaling pathway Covid-19: New data on Oxford AstraZeneca vaccine backs 12 week dosing interval Warnings to the potential COVID-19 transmission risk: vaccine is not enough Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Neutralizing Activity of BNT162b2-Elicited Serum Covid-19: Novavax vaccine efficacy is 86% against UK variant and 60% against South African variant Novavax offers first evidence that COVID vaccines protect people against variants Susceptibility of Circulating SARS-CoV-2 Variants to Neutralization Characteristics Associated With Racial/Ethnic Disparities in COVID-19 Outcomes in an Academic Health Care System Family violence against children in the wake of COVID-19 pandemic: a review of current perspectives and risk factors miR-137 mediates the functional link between c-Myc and EZH2 that regulates cisplatin resistance in ovarian cancer Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium Amino Acid Mutations Emerged in Spike Proteins of Six SARS-CoV-2 Strains We sincerely appreciate the authors, originating and submitting genetic sequences of SARS-CoV-2 and metadata made available through GISAID (https:// www.gisaid.org/).