A Peculiar Mutational Pattern in Omicron Variant of SARS-CoV-2 | [Pakistan Journal of Zoology • 2025]

Author(s):

1. Muhammad Tahir Khan: State Key Laboratory of Respiratory Disease, Guangzhou Key Laboratory of Tuberculosis Research, Department of Clinical Laboratory, Guangzhou Chest Hospital, Institute of Tuberculosis, Guangzhou Medical University, Guangzhou, China;Institute of Molecular Biology and Biotechnology, The University of Lahore. KM Defence Road, Lahore, Pakistan;Zhongjing Research and Industrialization Institute of Chinese Medicine, Zhongguancun Scientific Park, Meixi, Nanyang, Henan , PR China.

2. Madeeha Shehzad Lodhi: Institute of Molecular Biology and Biotechnology, The University of Lahore. KM Defence Road, Lahore, Pakistan

3. Irshad Ahmad: Department of Molecular Biology and Genetics. Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan

4. Arifa Mehreen: Department of Zoology, Wildlife and Fisheries, University of Agriculture Faisalabad. 6Department of Chemistry, Islamia College Peshawar, Peshawar, Pakistan

5. Nighat Nawaz: Department of Chemistry, Islamia College Peshawar, Peshawar , Pakistan

6. Muhammad Maisam: Institute of Molecular Biology and Biotechnology, The University of Lahore. KM Defence Road, Lahore, Pakistan

7. Atoofa Rukhsar: Institute of Molecular Biology and Biotechnology, The University of Lahore. KM Defence Road, Lahore, Pakistan

Abstract:

Evolutionary changes are continued in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and new variants of concern are emerging. The emergence of SARS-CoV-2 new Omicron variant and its rapid transmission in many countries ushered in a panic response. Here we analyzed the unique mutational pattern in Omicron through whole-genome sequence analysis, retrieved from different genomic databases worldwide. All the genomic sequences were analyzed for the Omicron variant using GISAID server. Mutations in targets protein were identified using CoVsurver. The most common mutation pattern in virus spike protein was analyzed for stability and flexibility effect using the machine learning algorithm of DynaMut server. A total of 337 genomes were identified as Omicron variants, reported from 23 countries. These sequences harbored some unique patterns of mutations, among which NSP14_I42>V, Spike_N969>K, Spike_N856>K, Spike_S371>L, Spike_L981>F, Spike_Q954>H, Membrane_Q19>E has been detected in 218 genomes. Spike mutations of this pattern, when analyzed for thermodynamic effect through DynaMut server, revealed that N969>K, N856>K, and S371>L are exhibiting stabilizing effects and gain in protein flexibility. Spike_L981>F seems destabilizing, but its impact on molecular flexibility appears to be increasing. The highest gain in flexibility on S proteins mutant has been observed due to mutation Q954>H, which almost affects the entire beta-sheet and loops of the spike C-terminal domain. The gain in flexibility may be supportive of virus adaptation and improved binding affinity with human angiotensin-converting enzyme 2 receptor protein. The second most common pattern NSP14_I42>V, Spike_N969>K, Spike_N856>K, Spike_S371>L, Spike_Q954>H, and Membrane_Q19>E was detected in 42 genomes. The enhanced stabilizing effect and molecular flexibility of most common patterns of Spike_N969>K, Spike_N856>K, and Spike_S371>L may possess higher infectivity and cell-to-cell transport than other SARS-CoV-2 variants. Further experimental validation is needed for a better understanding of the effect of these mutations on Omicron and vaccine efficacy. The current study provides valuable information for further experimental investigation of these mutations’ effects on virus transmission and disease severity

Page(s): 2133-2140

DOI: 10.17582/journal.pjz/20220911100910

Published: Journal: Pakistan Journal of Zoology, Volume: 57, Issue: 5, Year: 2025

Keywords:

SARSCoV2 , mutations , VOC , OMICRON , Spike

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