Baloch, Zulqarnain and Ikram, Aqsa and Hakim, Mohamad S. and Awan, Faryal Mehwish (2021) The impact of mutations on the pathogenic and antigenic activity of sars-cov-2 during the first wave of the covid-19 pandemic: A comprehensive immunoinformatics analysis. Vaccines, 9 (12). ISSN 2076393X
Full text not available from this repository. (Request a copy)Abstract
An in-depth analysis of first-wave SARS-CoV-2 genome is required to identify various mutations that significantly affect viral fitness. In the present study, we performed a comprehensive in silico mutational analysis of 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), and spike (S) proteins with the aim of gaining important insights into first-wave virus mutations and their functional and structural impact on SARS-CoV-2 proteins. Our integrated analysis gathered 6000 SARS-CoV-2 sequences and identified 92 mutations in S, 37 in RdRp, and 11 in 3CLpro regions. The impact of these mutations was also investigated using various in silico approaches. Among these, 32 mutations in S, 15 in RdRp, and 3 in 3CLpro proteins were found to be deleterious in nature and could alter the structural and functional behavior of the encoded proteins. The D614G mutation in spike and the P323Lmutation in RdRp are the globally dominant variants with a high frequency. Most of the identified mutations were also found in the binding moiety of the viral proteins which determine their critical involvement in host–pathogen interactions and may represent drug targets. Furthermore, potential CD4+ and CD8+ T cell epitopes were predicted, and their overlap with genetic variations was explored. This study also highlights several hot spots in which HLA and drug selective pressure overlap. The findings of the current study may allow a better understanding of COVID-19 diagnostics, vaccines, and therapeutics. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Item Type: | Article |
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Additional Information: | Cited by: 5; All Open Access, Gold Open Access, Green Open Access |
Uncontrolled Keywords: | coronavirus 3C protease; coronavirus spike glycoprotein; RNA directed RNA polymerase; viral protein; amino acid sequence; antigenicity; Article; binding affinity; coronavirus disease 2019; epitope mapping; gene frequency; gene mutation; gene sequence; human; immunoinformatics; ligand binding; mutational analysis; pandemic; protein stability; protein structure; sequence alignment; Severe acute respiratory syndrome coronavirus 2; single nucleotide polymorphism; structure activity relation; virus mutation |
Subjects: | R Medicine > RB Biomedical Sciences |
Divisions: | Faculty of Medicine, Public Health and Nursing > Biomedical Sciences |
Depositing User: | Sri JUNANDI |
Date Deposited: | 28 Sep 2024 04:05 |
Last Modified: | 28 Sep 2024 04:05 |
URI: | https://ir.lib.ugm.ac.id/id/eprint/4467 |