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Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses.
Gussow, Ayal B; Auslander, Noam; Faure, Guilhem; Wolf, Yuri I; Zhang, Feng; Koonin, Eugene V.
  • Gussow AB; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
  • Auslander N; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894; noam.auslander@nih.gov koonin@ncbi.nlm.nih.gov.
  • Faure G; Broad Institute of MIT and Harvard, Cambridge, MA 02142.
  • Wolf YI; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
  • Zhang F; Broad Institute of MIT and Harvard, Cambridge, MA 02142.
  • Koonin EV; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A ; 117(26): 15193-15199, 2020 06 30.
Article in English | MEDLINE | ID: covidwho-595720
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ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an immediate, major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe human pathogens. Using integrated comparative genomics and machine learning techniques, we identify key genomic features that differentiate SARS-CoV-2 and the viruses behind the two previous deadly coronavirus outbreaks, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), from less pathogenic coronaviruses. These features include enhancement of the nuclear localization signals in the nucleocapsid protein and distinct inserts in the spike glycoprotein that appear to be associated with high case fatality rate of these coronaviruses as well as the host switch from animals to humans. The identified features could be crucial contributors to coronavirus pathogenicity and possible targets for diagnostics, prognostication, and interventions.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Genome, Viral / Evolution, Molecular / Nucleocapsid Proteins / Spike Glycoprotein, Coronavirus / Betacoronavirus Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Genome, Viral / Evolution, Molecular / Nucleocapsid Proteins / Spike Glycoprotein, Coronavirus / Betacoronavirus Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2020 Document Type: Article