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. 2021 Oct 13:11:765039.
doi: 10.3389/fcimb.2021.765039. eCollection 2021.

Genomic Variations in the Structural Proteins of SARS-CoV-2 and Their Deleterious Impact on Pathogenesis: A Comparative Genomics Approach

Taj Mohammad  1 , Arunabh Choudhury  2 , Insan Habib  2 , Purva Asrani  3 , Yash Mathur  2 , Mohd Umair  2 , Farah Anjum  4 , Alaa Shafie  4 , Dharmendra Kumar Yadav  5 , Md Imtaiyaz Hassan  1
Affiliations

Genomic Variations in the Structural Proteins of SARS-CoV-2 and Their Deleterious Impact on Pathogenesis: A Comparative Genomics Approach

Taj Mohammad et al. Front Cell Infect Microbiol. .

Abstract

A continual rise in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease (COVID-19) has become a global threat. The main problem comes when SARS-CoV-2 gets mutated with the rising infection and becomes more lethal for humankind than ever. Mutations in the structural proteins of SARS-CoV-2, i.e., the spike surface glycoprotein (S), envelope (E), membrane (M) and nucleocapsid (N), and replication machinery enzymes, i.e., main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) creating more complexities towards pathogenesis and the available COVID-19 therapeutic strategies. This study analyzes how a minimal variation in these enzymes, especially in S protein at the genomic/proteomic level, affects pathogenesis. The structural variations are discussed in light of the failure of small molecule development in COVID-19 therapeutic strategies. We have performed in-depth sequence- and structure-based analyses of these proteins to get deeper insights into the mechanism of pathogenesis, structure-function relationships, and development of modern therapeutic approaches. Structural and functional consequences of the selected mutations on these proteins and their association with SARS-CoV-2 virulency and human health are discussed in detail in the light of our comparative genomics analysis.

Keywords: SARS-CoV-2 mutations; SARS-CoV-2 pathogenesis; coronavirus disease 2019; severe acute respiratory syndrome coronavirus-2; single amino acid substitutions.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Distribution of stabilizing and destabilizing mutations in SARS-CoV-2 Spike protein predicted by structure-based tools.
Figure 2
Figure 2
Distribution of stabilizing and destabilizing mutations in SARS-CoV-2 Envelope protein predicted by structure-based tools.
Figure 3
Figure 3
Distribution of stabilizing and destabilizing mutations in SARS-CoV-2 Main Protease predicted by structure-based tools.
Figure 4
Figure 4
Distribution of stabilizing and destabilizing mutations in SARS-CoV-2 Nucleocapsid protein predicted by structure-based tools.
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