Computational Analysis of the Accumulation of Mutations in Therapeutically Important RNA Viral Proteins During Pandemics with Special Emphasis on SARS-CoV-2

Sharma, A and Chandrashekar, CR and Krishna, S and Sowdhamini, R (2024) Computational Analysis of the Accumulation of Mutations in Therapeutically Important RNA Viral Proteins During Pandemics with Special Emphasis on SARS-CoV-2. In: Journal of Molecular Biology, 436 (19).

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Abstract

Single stranded RNA viruses are primary causative agents for pandemics, causing extensive morbidity and mortality worldwide. A pivotal question in pandemic preparedness and therapeutic intervention is what are the specific mutations which are more likely to emerge during such global health crises? This study aims to identify markers for mutations with the highest probability of emergence in these pandemics, focusing on the SARS-CoV-2 spike protein, an essential and therapeutically significant viral protein, starting from sequence information from the onset of the pandemic until July 2022. Quite consistently, we observed that emerged mutations tended to demonstrate a high genetic score, which reflects high similarity of the type of codon required for translation between an amino acid and to the mutated one. Further, this pattern is also observed in therapeutically significant proteins of other ssRNA pandemic viruses, including influenza (HA, NA), spike proteins of Ebola, envelope of Dengue and Chikungunya. We propose that the genetic score serves as an initial indicator, preceding the actual impact of the mutation on viral fitness. Finally, we developed a comprehensive computational pipeline to further explore and predict the subsequent effects of mutations on viral fitness. We believe that our pipeline can narrow down and predict future mutations in therapeutically important viral proteins during a pandemic. © 2024 The Authors

Item Type:	Journal Article
Publication:	Journal of Molecular Biology
Publisher:	Academic Press
Additional Information:	The copyright for this article belongs to the publisher.
Keywords:	coronavirus spike glycoprotein; proteome; viral protein, Article; binding affinity; bioinformatics; chikungunya; conformation; dengue; Ebolavirus; gene mutation; genetic distance; genetic risk score; host cell; human; immune response; immunocompromised patient; influenza; molecular dynamics; mutation accumulation; mutational analysis; nonhuman; pandemic; pathogenesis; protein stability; sequence alignment; sequence analysis; Severe acute respiratory syndrome coronavirus 2; virus entry; virus replication; virus transmission
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	18 Oct 2024 05:29
Last Modified:	18 Oct 2024 05:29
URI:	http://eprints.iisc.ac.in/id/eprint/86373

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