Tariq, Syeda Sumayya, Zia, Komal, Nur-e-Alam, Mohammad, Nerukh, Dmitry, Farafonov, Vladimir S. and Ul-Haq, Zaheer (2024). Impact of mutations in SARS-CoV-2 recombinant sub-variant XBB.1.16 on the binding affinity with human ACE2 receptor. Journal of Molecular Graphics and Modelling, 131 ,
Abstract
Despite the waning threat of the COVID-19 pandemic, its detrimental impact on global health persists. Regardless of natural immunity or immunity obtained through vaccination, emerging variants of the virus continue to undergo mutations and propagate globally. The persistent mutations in SARS-CoV-2, along with the subsequent formation of recombinant sub-variants has become a challenge for researchers and health professionals, raising concerns about the efficacy of current vaccines. Gaining a better understanding of the biochemical interactions between the Spike Protein (RBD) of SARS-CoV-2 variants and the human ACE2 receptor can prove to be beneficial in designing and developing antiviral therapeutics that are equally effective against all strains and emerging variants. Our objective in this study was to investigate the interfacial binding pattern of the SARS-CoV-2 RBD-ACE2 complex of the Wild Type (WT), Omicron, and the Omicron recombinant sub-variant XBB.1.16. We aimed to examine the atomic level factors and observe how mutations influence the interaction between the virus and its host using Molecular Dynamics simulation, MM/GBSA energy calculations, and Principal Component Analysis. Our findings reveal a higher degree of structural deviation and flexibility in XBB.1.16 compared to WT and Omicron. PCA indicated a wider cluster and significant flexibility in the movements of XBB.1.16 which can also be observed in free energy landscapes, while the normal mode analysis revealed converging motions within the RBD-ACE2 complexes which can facilitate the interaction between them. A pattern of decreased binding affinity was observed in case of XBB.1.16 when compared to the WT and Omicron. These observed deviations in XBB.1.16 when compared to its parent lineage Omicron, and WT can be attributed to the mutations specific to it. Collectively, these results enhance our understanding of the impact of mutations on the interaction between this strain and the host, taking us one step closer to designing effective antiviral therapeutics against the continually mutating strains.
Publication DOI: | https://doi.org/10.1016/j.jmgm.2024.108813 |
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Divisions: | College of Engineering & Physical Sciences > School of Computer Science and Digital Technologies > Applied Mathematics & Data Science College of Engineering & Physical Sciences > School of Computer Science and Digital Technologies College of Engineering & Physical Sciences > Systems analytics research institute (SARI) College of Engineering & Physical Sciences |
Funding Information: | The authors extend their appreciation to the Researchers Supporting Project number (RSPD2024R994), King Saud University, Riyadh, Saudi Arabia. Additionally, financial support from Higher Education Commission, Islamabad, Pakistan via Project No. 20–17602/N |
Additional Information: | Copyright © 2024 Elsevier Inc. This accepted manuscript version is licensed under the Creative Commons Attribution-NonCommercial License [https://creativecommons.org/licenses/by-nc/4.0/]. This license permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Uncontrolled Keywords: | COVID-19,RBD-ACE2 complex,SARS-CoV-2,XBB.1.16,Materials Chemistry,Spectroscopy,Physical and Theoretical Chemistry,Computer Graphics and Computer-Aided Design |
Publication ISSN: | 1873-4243 |
Data Access Statement: | Data will be made available on request. |
Last Modified: | 07 Oct 2024 07:58 |
Date Deposited: | 19 Jun 2024 16:16 |
Full Text Link: | |
Related URLs: |
https://www.sci ... 09332632400113X
(Publisher URL) http://www.scop ... tnerID=8YFLogxK (Scopus URL) |
PURE Output Type: | Article |
Published Date: | 2024-09 |
Published Online Date: | 2024-06-16 |
Accepted Date: | 2024-06-12 |
Authors: |
Tariq, Syeda Sumayya
Zia, Komal Nur-e-Alam, Mohammad Nerukh, Dmitry ( 0000-0001-9005-9919) Farafonov, Vladimir S. Ul-Haq, Zaheer |
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