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03 06, 2024;21 (1): 55.

Unraveling the genetic variations underlying virulence disparities among SARS-CoV-2 strains across global regions: insights from Pakistan.

Momina Jabeen, Shifa Shoukat, Huma Shireen, Yiming Bao, Abbas Khan, Amir Ali Abbasi
Author Information
  1. Momina Jabeen: National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, 45320, Islamabad, Pakistan.
  2. Shifa Shoukat: National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, 45320, Islamabad, Pakistan.
  3. Huma Shireen: National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, 45320, Islamabad, Pakistan.
  4. Yiming Bao: National Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, 100101, Beijing, China.
  5. Abbas Khan: Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China.
  6. Amir Ali Abbasi: National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, 45320, Islamabad, Pakistan. abbasiam@qau.edu.pk.
PMID: 38449001 DOI: 10.1186/s12985-024-02328-8

Abstract

Over the course of the COVID-19 pandemic, several SARS-CoV-2 variants have emerged that may exhibit different etiological effects such as enhanced transmissibility and infectivity. However, genetic variations that reduce virulence and deteriorate viral fitness have not yet been thoroughly investigated. The present study sought to evaluate the effects of viral genetic makeup on COVID-19 epidemiology in Pakistan, where the infectivity and mortality rate was comparatively lower than other countries during the first pandemic wave. For this purpose, we focused on the comparative analyses of 7096 amino-acid long polyprotein pp1ab. Comparative sequence analysis of 203 SARS-CoV-2 genomes, sampled from Pakistan during the first wave of the pandemic revealed 179 amino acid substitutions in pp1ab. Within this set, 38 substitutions were identified within the Nsp3 region of the pp1ab polyprotein. Structural and biophysical analysis of proteins revealed that amino acid variations within Nsp3's macrodomains induced conformational changes and modified protein-ligand interactions, consequently diminishing the virulence and fitness of SARS-CoV-2. Additionally, the epistatic effects resulting from evolutionary substitutions in SARS-CoV-2 proteins may have unnoticed implications for reducing disease burden. In light of these findings, further characterization of such deleterious SARS-CoV-2 mutations will not only aid in identifying potential therapeutic targets but will also provide a roadmap for maintaining vigilance against the genetic variability of diverse SARS-CoV-2 strains circulating globally. Furthermore, these insights empower us to more effectively manage and respond to potential viral-based pandemic outbreaks of a similar nature in the future.

Keywords

COVID-19 Macrodomains Nsp3 SARS-CoV-2 Viral fitness pp1ab polyprotein

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MeSH Term

Humans
SARS-CoV-2
COVID-19
Pakistan
Pandemics
Virulence
Amino Acids
Polyproteins
Genetic Variation

Chemicals

Amino Acids
Polyproteins
Journal Article

Word Cloud

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