SARS-CoV-2 omicron RBD forms a weaker binding affinity to hACE2 compared to Delta RBD in in-silico studies

Abstract

The COVID-19 pandemic sparked an unprecedented race in biotechnology in a search for effective therapies and a preventive vaccine. The continued appearance of SARS-CoV-2 variants of concern (VoCs) further swept the world. The entry of SARS-CoV-2 into cells is mediated by binding the receptor-binding domain (RBD) of the S protein to the cell-surface receptor, human angiotensin-converting enzyme 2 (hACE2). In this study, using a coarse-grained force field to parameterize the system, we employed steered-molecular dynamics (SMD) simulations to reveal the binding of SARS-CoV-2 Delta/Omicron RBD to hACE2. Our benchmarked results demonstrate a good correlation between computed rupture force and experimental binding free energy for known protein-protein systems. Moreover, our findings show that the Omicron RBD has a weaker binding affinity to hACE2, consistent with the respective experimental results. This indicates that our method can effectively be applied to other emerging SARS-CoV-2 strains.

Communicated by Ramaswamy H. Sarma

Keywords:

• RBD
• hACE2
• steered-molecular dynamics
• coarse-grained model

Acknowledgements

We especially thank Dr. Son Tung Ngo at the Laboratory of Theoretical and Computational Biophysics, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh City, Vietnam, for comments and valuable discussion.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

Conceptualization: HTTP and LHT; Data curation: THL and LHT; Formal analysis: THL; Methodology: THL and LHT; Resources: LHT; Supervision: HTTP; Validation: LHT and HTTP; Visualization: THL; Roles/Writing - original draft: HTTP; Writing - review & editing: THL, LHT, and HTTP.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.