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Updated: Oct 12, 2025

Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Mechanistic insights into the effects of key mutations on SARS-CoV-2 RBD-ACE2 binding
Abhishek Aggarwal1, Supriyo Naskar1, Nikhil Maroli1
1Center for Condensed Matter Theory, Department of Physics, Indian Institute of Science, Bangalore 560012, India. maiti@iisc.ac.in.
Abstract:
Some recent SARS-CoV-2 variants appear to have increased transmissibility compared to the original strain. An underlying mechanism could be the improved ability of the variants to bind receptors on the target cells and infect them. In this study, we provide atomic-level insights into the binding of the receptor binding domain (RBD) of the wild-type SARS-CoV-2 spike protein and its single (N501Y), double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants to the human ACE2 receptor. Using extensive all-atom molecular dynamics simulations and advanced free energy calculations, we estimate the associated binding affinities and binding hotspots. We observe significant secondary structural changes in the RBD of the mutants, which lead to different binding affinities. We find higher binding affinities for the double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants than for the wild type and the N501Y variant, which could contribute to the higher transmissibility of recent variants containing these mutations.
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