Computational Analysis of the accumulation of mutations in therapeutically important RNA viral proteins during pandemics with special emphasis on SARS-CoV-2.

Publication date: Jul 22, 2024

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.

Open Access PDF

Concepts Keywords
Comprehensive Computational
Genetic Cov
July Genetic
Pandemic High
Viruses Important
Mutations
Observed
Pandemic
Pandemics
Protein
Sars
Significant
Spike
Viral
Viruses

Semantics

Type Source Name
disease VO Viruses
disease MESH morbidity
disease IDO intervention
pathway REACTOME Translation
disease MESH influenza
disease MESH Dengue
disease MESH mutation rate
disease IDO host
disease VO effective
disease IDO replication
drug DRUGBANK Amino acids
disease MESH point mutation
drug DRUGBANK L-Tryptophan
drug DRUGBANK L-Arginine
drug DRUGBANK L-Cysteine
disease VO vaccine
disease MESH aids
disease VO time
disease IDO algorithm
disease VO Gap
disease VO frequency
drug DRUGBANK Cysteamine
disease MESH uncertainty
drug DRUGBANK Pixantrone
drug DRUGBANK Aspartame
drug DRUGBANK L-Alanine
drug DRUGBANK L-Aspartic Acid
disease IDO immune response
drug DRUGBANK Diethylstilbestrol
disease IDO quality
drug DRUGBANK Coenzyme M
disease MESH COVID 19
disease VO population
drug DRUGBANK Serine
drug DRUGBANK L-Leucine
disease MESH Mumps
disease MESH immunocompromised patient
disease VO Yellow fever virus
drug DRUGBANK Proline

Original Article

(Visited 3 times, 1 visits today)