Computational prediction of the effect of mutations in the receptor-binding domain on the interaction between SARS-CoV-2 and human ACE2.
Mol Divers
; 26(6): 3309-3324, 2022 Dec.
Article
in English
| MEDLINE | ID: covidwho-1681347
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 continues to mutate. Numerous studies have indicated that this viral mutation, particularly in the receptor-binding domain area, may increase the viral affinity for human angiotensin-converting enzyme 2 (hACE2), the receptor for viral entry into host cells, thereby increasing viral virulence and transmission. In this study, we investigated the binding affinity of SARS-CoV-2 variants (Delta plus, Iota, Kappa, Mu, Lambda, and C.1.2) on hACE2 using computational modeling with a protein-protein docking approach. The simulation results indicated that there were differences in the interactions between the RBD and hACE2, including hydrogen bonding, salt bridge interactions, non-bonded interactions, and binding free energy differences among these variants. Molecular dynamics simulations revealed that mutations in the RBD increase the stability of the hACE2-spike protein complex relative to the wild type, following the global stability trend and increasing the binding affinity. The value of binding-free energy calculated using molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) indicated that all mutations in the spike protein increased the contagiousness of SARS-CoV-2 variants. The findings of this study provide a foundation for developing effective interventions against these variants. Computational modeling elucidates that the spike protein of SARS-CoV-2 variants binds considerably stronger than the wild-type to hACE2.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Angiotensin-Converting Enzyme 2
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Mol Divers
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
Affiliation country:
S11030-022-10392-x
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