In silico analysis of SARS-CoV-2 spike protein N501Y and N501T mutation effects on human ACE2 binding.
J Mol Graph Model
; 116: 108260, 2022 Nov.
Article
in English
| MEDLINE | ID: covidwho-1914639
ABSTRACT
The SARS-CoV-2 is an RNA-based virus and the most vital step of its survival is the attachment to hACE2 through its spike protein. Although SARS-CoV-2 has the ability to maintain high accurate replication and it can be accepted as a low mutation risked virus, it already showed more than nine thousand mutations in spike protein, of which 44 mutations are located within a 3.2 Å interacting distance from the hACE2 receptor. Mutations on spike protein, N501Y and N501T raised serious concerns for higher transmissibility and resistance towards current vaccines. In the current study, the mutational outcomes of N501Y and N501T on the hACE2-SARS CoV-2 spike protein complexation were analyzed by employing all-atom classic molecular dynamics (MD) simulations. These simulations revealed that both N501Y and N501T mutations increased the binding strength of spike protein to the host hACE2, predicted by binding free energy analysis via MM/GBSA rescoring scheme. This study highlights the importance of energy-based analysis for identifying mutational outcomes and will shed light on handling long-term and effective treatment strategies including repurposing anti-viral drugs, anti-SARS-CoV-2 antibodies, vaccines, and antisense based-therapies.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Spike Glycoprotein, Coronavirus
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
J Mol Graph Model
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
Affiliation country:
J.jmgm.2022.108260
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