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      A Critical Analysis of the Evidence for the SARS-CoV-2 Origin Hypotheses

      editorial
      a , b , c , b , d , b , e , , f
      Journal of Virology
      American Society for Microbiology
      COVID-19, SARS-CoV-2, zoonosis, coronavirus, lab leak, origin

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          ABSTRACT

          When humans experience a new, devastating viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant challenges arise. How should individuals as well as societies respond to the situation? One of the primary questions concerns the origin of the SARS-CoV-2 virus that infected and was transmitted efficiently among humans, resulting in a pandemic. At first glance, the question appears straightforward to answer. However, the origin of SARS-CoV-2 has been the topic of substantial debate primarily because we do not have access to some relevant data. At least two major hypotheses have been suggested: a natural origin through zoonosis followed by sustained human-to-human spread or the introduction of a natural virus into humans from a laboratory source. Here, we summarize the scientific evidence that informs this debate to provide our fellow scientists and the public with the tools to join the discussion in a constructive and informed manner. Our goal is to dissect the evidence to make it more accessible to those interested in this important problem. The engagement of a broad representation of scientists is critical to ensure that the public and policy-makers can draw on relevant expertise in navigating this controversy.

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          Most cited references33

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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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            Bats are natural reservoirs of SARS-like coronaviruses.

            Severe acute respiratory syndrome (SARS) emerged in 2002 to 2003 in southern China. The origin of its etiological agent, the SARS coronavirus (SARS-CoV), remains elusive. Here we report that species of bats are a natural host of coronaviruses closely related to those responsible for the SARS outbreak. These viruses, termed SARS-like coronaviruses (SL-CoVs), display greater genetic variation than SARS-CoV isolated from humans or from civets. The human and civet isolates of SARS-CoV nestle phylogenetically within the spectrum of SL-CoVs, indicating that the virus responsible for the SARS outbreak was a member of this coronavirus group.
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              Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic

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                Author and article information

                Contributors
                Role: Editor in Chief, mBio
                Role: Editor in Chief, Journal of Virology
                Role: Editor in Chief, mSphere
                Journal
                J Virol
                J Virol
                jvi
                Journal of Virology
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                0022-538X
                1098-5514
                28 March 2023
                April 2023
                28 March 2023
                : 97
                : 4
                : e00365-23
                Affiliations
                [a ] Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
                [b ] Department of Immunobiology, University of Arizona, Tucson, Arizona, USA
                [c ] Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
                [d ] Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA
                [e ] BIO5 Institute, University of Arizona, Tucson, Arizona, USA
                [f ] Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
                Author notes

                The authors declare no conflict of interest.

                Author information
                https://orcid.org/0000-0001-9968-8586
                https://orcid.org/0000-0002-6646-7290
                Article
                00365-23 jvi.00365-23
                10.1128/jvi.00365-23
                10134824
                36897089
                4e9ef97c-5f9d-4b30-b21b-d6780239d84a
                Copyright © 2023 Alwine et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 33, Pages: 7, Words: 5153
                Categories
                Editorial
                virology, Virology
                Custom metadata
                April 2023

                Microbiology & Virology
                covid-19,sars-cov-2,zoonosis,coronavirus,lab leak,origin
                Microbiology & Virology
                covid-19, sars-cov-2, zoonosis, coronavirus, lab leak, origin

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