Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses.
Animals
Betacoronavirus
/ classification
Evolution, Molecular
Genome, Viral
Host Specificity
Humans
Machine Learning
Middle East Respiratory Syndrome Coronavirus
/ classification
Mutagenesis, Insertional
Nuclear Localization Signals
/ genetics
Nucleocapsid Proteins
/ chemistry
Phylogeny
SARS-CoV-2
Sequence Homology
Spike Glycoprotein, Coronavirus
/ chemistry
Virulence
/ genetics
COVID-19
coronaviruses
nucleocapsid
pathogenicity
spike protein
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
30 06 2020
30 06 2020
Historique:
pubmed:
12
6
2020
medline:
18
7
2020
entrez:
12
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32522874
pii: 2008176117
doi: 10.1073/pnas.2008176117
pmc: PMC7334499
doi:
Substances chimiques
Nuclear Localization Signals
0
Nucleocapsid Proteins
0
Spike Glycoprotein, Coronavirus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15193-15199Subventions
Organisme : NHLBI NIH HHS
ID : DP1 HL141201
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110049
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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