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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.

Titel:	Unraveling the genetic variations underlying virulence disparities among SARS-CoV-2 strains across global regions: insights from Pakistan.
Autor/in / Beteiligte Person:	Jabeen, M ; Shoukat, S ; Shireen, H ; Bao, Y ; Khan, A ; Abbasi, AA
Link:	Full Text Finder (Volltext)
Zeitschrift:	Virology journal, Jg. 21 (2024-03-06), Heft 1, S. 55
Veröffentlichung:	[London] : BioMed Central, 2004-, 2024
Medientyp:	academicJournal
ISSN:	1743-422X (electronic)
DOI:	10.1186/s12985-024-02328-8
Schlagwort:	Humans Pakistan epidemiology Pandemics Virulence genetics Amino Acids Polyproteins Genetic Variation SARS-CoV-2 genetics COVID-19 epidemiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Virol J] 2024 Mar 06; Vol. 21 (1), pp. 55. <i>Date of Electronic Publication: </i>2024 Mar 06. MeSH Terms: SARS-CoV-2* / genetics ; COVID-19* / epidemiology ; Humans ; Pakistan / epidemiology ; Pandemics ; Virulence / genetics ; Amino Acids ; Polyproteins ; Genetic Variation References: Virology. 2015 Oct;484:313-322. (PMID: 26149721) ; Int J Infect Dis. 2020 Jul;96:459-460. (PMID: 32464271) ; J Chem Theory Comput. 2013 Sep 10;9(9):3878-88. (PMID: 26592383) ; Trends Microbiol. 2018 Jul;26(7):598-610. (PMID: 29268982) ; Int J Biol Macromol. 2022 May 31;208:105-125. (PMID: 35300999) ; Nucleic Acids Res. 2021 Jul 21;49(13):7695-7712. (PMID: 34232992) ; Protein Sci. 2018 Jan;27(1):135-145. (PMID: 28884485) ; Science. 2007 Sep 14;317(5844):1544-8. (PMID: 17702911) ; Protein Eng. 1995 Feb;8(2):127-34. (PMID: 7630882) ; Protein Sci. 1993 Sep;2(9):1511-9. 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(PMID: 29128390) Contributed Indexing: Keywords: COVID-19; Macrodomains; Nsp3; SARS-CoV-2; Viral fitness; pp1ab polyprotein Substance Nomenclature: 0 (Amino Acids) ; 0 (Polyproteins) SCR Organism: SARS-CoV-2 variants Entry Date(s): Date Created: 20240306 Date Completed: 20240308 Latest Revision: 20240513 Update Code: 20240514 PubMed Central ID: PMC10916261

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