Molecular dynamics of SARS-CoV-2 omicron variants from Philippine isolates against hesperidin as spike protein inhibitor

College

College of Science

Department/Unit

Chemistry

Document Type

Article

Source Title

Biophysical Chemistry

Volume

318

Publication Date

2025

Abstract

SARS-CoV-2 remains a global threat with new sublineages posing challenges, particularly in the Philippines. Hesperidin (HD) is being studied as a potential prophylactic for COVID-19. However, the virus’s rapid evolution could alter how HD binds to it, affecting its effectiveness. Here, we study the mutation-induced variabilities of HD dynamics and their effects on molecular energetics in SARS-CoV-2 spike receptor complex systems. We considered eight different point mutations present in the Omicron variant. Root-mean-square deviation and binding energy analysis showed that S477N and Omicron did not eject HD throughout the simulation. Hydrogen bond distribution analysis highlighted the involvement of hydrogen bonding in mutant-HD stabilization, espe- cially for S477N and Omicron. Root-mean-square fluctuation analysis revealed evidence of Y505H destabiliza- tion on complex systems, while distal-end loop mutations increased loop flexibility for all models bearing the three mutations. Per-residue energy decomposition demonstrated that Q493R substitution increased HD inter- action. Free energy landscape and essential dynamics through principal component analysis provided insights into the conformational subspace distribution of mutant model molecular dynamics trajectories. In conclusion, significant mutations contributed to the HD interaction in different ways. S477N has shown significant binding contributions through favorable ligand interaction, while other mutations contribute via conformational modi- fications, increased affinity due to sidechain mutations, and increased loop flexibility.

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Digitial Object Identifier (DOI)

10.1016/j.bpc.2024.107387

Disciplines

Chemistry

Keywords

COVID-19 (Disease)--Philippines; Hesperidin; Molecular dynamics

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