Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity.
Microorganisms
; 9(11)2021 Nov 11.
Article
in English
| MEDLINE | ID: covidwho-1512502
ABSTRACT
Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known how these mutations affect the binding of RBD to GRP78. The current study provides a structural basis for the binding of GRP78 to the different variants, i.e., B.1.1.7, B.1.351, B.1.617, and P.1 (spike RBD), of SARS-CoV-2 using a biomolecular simulation approach. Docking results showed that the new variants bound stronger than the wild-type, which was further confirmed through the free energy calculation results. All-atom simulation confirmed structural stability, which was consistent with previous results by following the global stability trend. We concluded that the increased binding affinity of the B.1.1.7, B.1.351, and P.1 variants was due to a variation in the bonding network that helped the virus induce a higher infectivity and disease severity. Consequently, we reported that the aforementioned new variants use GRP78 as an alternate receptor to enhance their seriousness.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Prognostic study
Topics:
Variants
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Microorganisms9112331
Similar
MEDLINE
...
LILACS
LIS