Unravelling the link between SARS-CoV-2 mutation frequencies, patient comorbidities, and structural dynamics.

Autor: Azzeri A; Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Negeri Sembilan, Malaysia., Mohamed NA; Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Negeri Sembilan, Malaysia., Wan Rosli SH; Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Negeri Sembilan, Malaysia., Abdul Samat MN; Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia., Rashid ZZ; Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia., Mohamad Jamali MA; Faculty of Science and Technology, Universiti Sains Islam Malaysia, Nilai, Negeri Sembilan, Malaysia., Md Zoqratt MZH; Fast Genomics Solutions, Subang Jaya, Selangor Darul Ehsan, Malaysia.; School of Science, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia., Mohammad Nasir MA; Fast Genomics Solutions, Subang Jaya, Selangor Darul Ehsan, Malaysia.; School of Science, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia., Ranjit Singh HK; Fast Genomics Solutions, Subang Jaya, Selangor Darul Ehsan, Malaysia.; School of Science, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia., Azmi L; Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Negeri Sembilan, Malaysia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Mar 14; Vol. 19 (3), pp. e0291892. Date of Electronic Publication: 2024 Mar 14 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0291892
Abstrakt: Genomic surveillance is crucial for tracking emergence and spread of novel variants of pathogens, such as SARS-CoV-2, to inform public health interventions and to enforce control measures. However, in some settings especially in low- and middle- income counties, where sequencing platforms are limited, only certain patients get to be selected for sequencing surveillance. Here, we show that patients with multiple comorbidities potentially harbour SARS-CoV-2 with higher mutation rates and thus deserve more attention for genomic surveillance. The relationship between the patient comorbidities, and type of amino acid mutations was assessed. Correlation analysis showed that there was a significant tendency for mutations to occur within the ORF1a region for patients with higher number of comorbidities. Frequency analysis of the amino acid substitution within ORF1a showed that nsp3 P822L of the PLpro protease was one of the highest occurring mutations. Using molecular dynamics, we simulated that the P822L mutation in PLpro represents a system with lower Root Mean Square Deviation (RMSD) fluctuations, and consistent Radius of gyration (Rg), Solvent Accessible Surface Area (SASA) values-indicate a much stabler protein than the wildtype. The outcome of this study will help determine the relationship between the clinical status of a patient and the mutations of the infecting SARS-CoV-2 virus.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Azzeri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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