John Mekalanos, Ph.D.
Adele Lehman Professor of Microbiology & Molecular Genetics
Department of Microbiology
Harvard Medical School

Protein covariance networks reveal interactions important to the emergence of SARS coronaviruses as human pathogens

SARS-CoV-2 is one of three recognized coronaviruses (CoVs) that have caused epidemics or pandemics in the 21st century and that likely emerged from animal reservoirs based on genomic similarities to bat and civet viruses. Here we report the analysis of conserved interactions between amino acid residues in all proteins encoded by SARS-CoV-related viruses. We identified pairs and networks of residue variants that exhibited statistically high frequencies of covariance with each other. While these interactions are likely key to both protein structure and other protein-protein interactions, we have also found that they can be used for understanding viral evolution and adaptation. Our data provide evidence that the evolutionary processes that converted a bat virus into human pathogen occurred through recombination with other viruses in combination with new adaptive mutations important for entry into human cells.

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