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

Van A. Ngo; Ramesh K. Jha

doi:10.1371/journal.pone.0257905

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

Van A. Ngo, Ramesh K. Jha

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English
Article number	e0257905
Journal	PLoS ONE
Volume	16
Issue number	9 September
DOIs	https://doi.org/10.1371/journal.pone.0257905
State	Published - Sep 2021
Externally published	Yes

Funding

The research was supported by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on response to COVID-19, with funding provided by the Coronavirus CARES Act. V.A.N is a Director’s Postdoctoral Fellow at LANL and is partially funded by Laboratory Directed R&D Postdoctoral Research and Development fellowship (20170692PRD4). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funders	Funder number
Laboratory Directed R&D Postdoctoral Research and Development	20170692PRD4
National Virtual Biotechnology Laboratory
U.S. Department of Energy
Office of Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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abstract = "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.",

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

Abstract

Funding

UN SDGs

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