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. 2022 Feb;40(3):1205-1215.
doi: 10.1080/07391102.2020.1823885. Epub 2020 Sep 23.

Identification of destabilizing SNPs in SARS-CoV2-ACE2 protein and spike glycoprotein: implications for virus entry mechanisms

Zoya Khalid  1 , Hammad Naveed  1
Affiliations

Identification of destabilizing SNPs in SARS-CoV2-ACE2 protein and spike glycoprotein: implications for virus entry mechanisms

Zoya Khalid et al. J Biomol Struct Dyn. 2022 Feb.

Abstract

COVID-19 an outbreak of a novel corona virus originating from Wuhan, China in December 2019 has now spread across the entire world and has been declared a pandemic by WHO. Angiotensin converting enzyme 2 (ACE2) is a receptor protein that interacts with the spike glycoprotein of the host to facilitate the entry of coronavirus (SARS-CoV-2) hence causing the disease (COVID-19). Our experimental design is based on bioinformatics approach that combines sequence, structure and consensus based tools to label a protein coding single nucleotide polymorphism (SNP) as damaging/deleterious or neutral. The interaction of wildtype ACE2-spike glycoprotein and their variants were analyzed using docking studies. The mutations W461R, G405E and F588S in ACE2 receptor protein and population specific mutations P391S, C12S and G1223A in the spike glycoprotein were predicted as highly destabilizing to the structure of the bound complex. So far, no extensive in silico study has been reported that identifies the effect of SNPs on Spike glycoprotein-ACE2 interaction exploring both sequence and structural features. To this end, this study conducted an in-depth analysis that facilitates in identifying the mutations that blocks the interaction of two proteins that can result in stopping the virus from entering the host cell.Communicated by Ramaswamy H. Sarma.

Keywords: 2019-nCOV; ACE2; COVID-19; SNPs; spike glycoprotein.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
An overview of the methodology design of nsSNPs structure-function analysis.
Figure 2.
Figure 2.
(A) Structural position of the ACE2 mutants G405E, F588S and W461R in the protein 3D structure visualized in PyMol. (B) Structural position of population specific mutations of spike glycoprotein, P391S, C12S and G1223A in the protein 3D model visualized in PyMol.
Figure 3.
Figure 3.
(A) Docked complex of wild type 2019-nCoV spike glycoprotein with wild type ACE2 receptor protein. (B) The docked complex of 2019-nCoV spike glycoprotein with mutant G405E ACE2 receptor. (C) The docked complex of 2019-nCoV spike glycoprotein with mutant W461R ACE2 receptor.(D) The docked complex of 2019-nCoV spike glycoprotein with mutant F588S ACE2 receptor. (E) The docked complex of mutant 2019-nCoV spike glycoprotein P391S with wild type ACE2. (F) The docked complex of mutant 2019-nCoV spike glycoprotein C12S with wild type ACE2. (G) The docked complex of mutant 2019-nCoV spike glycoprotein G1223A with wild type ACE2.
Figure 3.
Figure 3.
(A) Docked complex of wild type 2019-nCoV spike glycoprotein with wild type ACE2 receptor protein. (B) The docked complex of 2019-nCoV spike glycoprotein with mutant G405E ACE2 receptor. (C) The docked complex of 2019-nCoV spike glycoprotein with mutant W461R ACE2 receptor.(D) The docked complex of 2019-nCoV spike glycoprotein with mutant F588S ACE2 receptor. (E) The docked complex of mutant 2019-nCoV spike glycoprotein P391S with wild type ACE2. (F) The docked complex of mutant 2019-nCoV spike glycoprotein C12S with wild type ACE2. (G) The docked complex of mutant 2019-nCoV spike glycoprotein G1223A with wild type ACE2.
See this image and copyright information in PMC

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