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      SARS-CoV-2 one year on: evidence for ongoing viral adaptation

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          Abstract

          SARS-CoV-2 is thought to have originated in the human population from a zoonotic spillover event. Infection in humans results in a variety of outcomes ranging from asymptomatic cases to the disease COVID-19, which can have significant morbidity and mortality, with over two million confirmed deaths worldwide as of January 2021. Over a year into the pandemic, sequencing analysis has shown that variants of SARS-CoV-2 are being selected as the virus continues to circulate widely within the human population. The predominant drivers of genetic variation within SARS-CoV-2 are single nucleotide polymorphisms (SNPs) caused by polymerase error, potential host factor driven RNA modification, and insertion/deletions (indels) resulting from the discontinuous nature of viral RNA synthesis. While many mutations represent neutral ‘genetic drift’ or have quickly died out, a subset may be affecting viral traits such as transmissibility, pathogenicity, host range, and antigenicity of the virus. In this review, we summarise the current extent of genetic change in SARS-CoV-2, particularly recently emerging variants of concern, and consider the phenotypic consequences of this viral evolution that may impact the future trajectory of the pandemic.

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

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

            Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260
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              Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

              Summary The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.
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                Author and article information

                Journal
                J Gen Virol
                J Gen Virol
                jgv
                jgv
                The Journal of General Virology
                Microbiology Society
                0022-1317
                1465-2099
                2021
                15 April 2021
                15 April 2021
                : 102
                : 4
                : 001584
                Affiliations
                [ 1] departmentDepartment of Infectious Diseases, St Marys Medical School , Imperial College London , UK
                [ 2] departmentInstitute of Infection, Veterinary and Ecology Sciences , University of Liverpool , UK
                [ 3] departmentA*STAR Infectious Diseases Laboratories (A*STAR ID Labs) , Agency for Science, Technology and Research (A*STAR) , Singapore
                Author notes
                *Correspondence: Wendy S. Barclay, w.barclay@ 123456imperial.ac.uk
                Author information
                https://orcid.org/0000-0001-7077-2928
                https://orcid.org/0000-0002-0653-2097
                https://orcid.org/0000-0002-6582-0275
                https://orcid.org/0000-0002-3948-0895
                Article
                001584
                10.1099/jgv.0.001584
                8290271
                33855951
                64621b13-017f-4708-940d-a0709591e567
                © 2021 The Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.

                History
                : 24 January 2021
                : 16 March 2021
                Funding
                Funded by: Biotechnology and Biological Sciences Research Council
                Award ID: BB/S008292/1
                Award Recipient : WendyS. Barclay
                Funded by: Biotechnology and Biological Sciences Research Council
                Award ID: BB/K002465/1
                Award Recipient : WendyS. Barclay
                Funded by: Wellcome Trust
                Award ID: 205100
                Award Recipient : WendyS. Barclay
                Funded by: U.S. Food and Drug Administration
                Award ID: 75F40120C00085
                Award Recipient : JulianA. Hiscox
                Funded by: Medical Research Council
                Award ID: MR/N013840/1
                Award Recipient : RebekahPenrice-Randal
                Funded by: Biotechnology and Biological Sciences Research Council
                Award ID: BB/R013071/1
                Award Recipient : ThomasPhilip Peacock
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                Microbiology & Virology
                sars-cov-2,covid-19,coronavirus,mutant,adaptation,pandemic
                Microbiology & Virology
                sars-cov-2, covid-19, coronavirus, mutant, adaptation, pandemic

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