Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction

Journal Article · 28 September 2021 · PLoS ONE

DOI: https://doi.org/10.1371/journal.pone.0257905 · OSTI ID:1828714

Ngo, Anh Van  ^[1]; Jha, Ramesh Kumar  ^[1]

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1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

SARS-CoV-2 virus, the causative agent of Covid-19, has fired up a global pandemic. The virus interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) for an invasion via receptor binding domain (RBD) on its spike protein. To provide a deeper understanding of this interaction, we performed microsecond simulations of the RBD-ACE2 complex for SARS-CoV-2 and compared it with the closely related SARS-CoV discovered in 2003. We show residues in the RBD of SARS-CoV-2 that were mutated from SARS-CoV, collectively help make the RBD anchor much stronger to the N-terminal part of ACE2 than the corresponding residues on RBD of SARS-CoV. This would result in a reduced dissociation rate of SARS-CoV-2 from human receptor protein compared to SARS-CoV. The phenomenon was consistently observed in simulations beyond 500 ns and was reproducible across different force fields. Altogether, our study adds more insight into the critical dynamics of the key residues at the virus spike and human receptor binding interface and potentially aids the development of diagnostics and therapeutics to combat the pandemic efficiently.

• Research Organization: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER)
• Grant/Contract Number: 89233218CNA000001
• OSTI ID: 1828714
• Report Number(s): LA-UR--20-24876
• Journal Information: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 9 Vol. 16; ISSN 1932-6203
• Publisher: Public Library of ScienceCopyright Statement
• Country of Publication: United States
• Language: English