Computational analysis of affinity dynamics between the variants of SARS-CoV-2 spike protein (RBD) and human ACE-2 receptor.

Autor: Sultana N; Department of Plant Biotechnology, University of Agricultural Sciences, GKVK, Bangalore, 560 065, India., Nagesha SN; Department of Plant Biotechnology, College of Agriculture, Hassan, UAS, Bangalore, 573 225, India. nageshasn@uasbangalore.edu.in., Reddy CNL; Department of Plant Pathology, University of Agricultural Sciences, GKVK, Bangalore, 560 065, India., Ramesh BN; ICAR-PHT, UAS, GKVK, Bangalore, 560 065, India., Shyamalamma S; Department of Plant Biotechnology, University of Agricultural Sciences, GKVK, Bangalore, 560 065, India., Shashidhara KS; Department of Genetics and Plant Breeding, College of Agriculture, Hassan, UAS, Bangalore, 573 225, India., Satish KM; Department Biotechnology, KSNUAHS, Shivamogga, 577 412, India., Pradeep C; Department of Plant Biotechnology, University of Agricultural Sciences, GKVK, Bangalore, 560 065, India., Vidyadhar GD; Department of Plant Biotechnology, University of Agricultural Sciences, GKVK, Bangalore, 560 065, India.
Jazyk: angličtina
Zdroj: Virology journal [Virol J] 2024 Apr 19; Vol. 21 (1), pp. 88. Date of Electronic Publication: 2024 Apr 19.
DOI: 10.1186/s12985-024-02365-3
Abstrakt: The novel coronavirus SARS-CoV-2 resulted in a significant worldwide health emergency known as the COVID-19 pandemic. This crisis has been marked by the widespread of various variants, with certain ones causing notable apprehension. In this study, we harnessed computational techniques to scrutinize these Variants of Concern (VOCs), including various Omicron subvariants. Our approach involved the use of protein structure prediction algorithms and molecular docking techniques, we have investigated the effects of mutations within the Receptor Binding Domain (RBD) of SARS-CoV-2 and how these mutations influence its interactions with the human angiotensin-converting enzyme 2 (hACE-2) receptor. Further we have predicted the structural alterations in the RBD of naturally occurring SARS-CoV-2 variants using the tr-Rosetta algorithm. Subsequent docking and binding analysis employing HADDOCK and PRODIGY illuminated crucial interactions occurring at the Receptor-Binding Motif (RBM). Our findings revealed a hierarchy of increased binding affinity between the human ACE2 receptor and the various RBDs, in the order of wild type (Wuhan-strain) < Beta < Alpha < Gamma < Omicron-B.1.1.529 < Delta < Omicron-BA.2.12.1 < Omicron-BA.5.2.1 < Omicron-BA.1.1. Notably, Omicron-BA.1.1 demonstrated the highest binding affinity of -17.4 kcal mol -1 to the hACE2 receptor when compared to all the mutant complexes. Additionally, our examination indicated that mutations occurring in active residues of the Receptor Binding Domain (RBD) consistently improved the binding affinity and intermolecular interactions in all mutant complexes. Analysis of the differences among variants has laid a foundation for the structure-based drug design targeting the RBD region of SARS-CoV-2.
(© 2024. The Author(s).)
Databáze: MEDLINE
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