Open AccessGenomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses
Author(s) -
Ayal B. Gussow,
Noam Auslander,
Guilhem Faure,
Yuri I. Wolf,
Feng Zhang,
Eugene V. Koonin
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2008176117
Subject(s) - coronavirus , biology , middle east respiratory syndrome coronavirus , virology , pathogenicity , betacoronavirus , genome , genomics , middle east respiratory syndrome , outbreak , covid-19 , case fatality rate , pandemic , computational biology , genetics , gene , medicine , infectious disease (medical specialty) , microbiology and biotechnology , disease , epidemiology , pathology
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.