Investigating the binding affinity of andrographolide against human SARS-CoV-2 spike receptor-binding domain through docking and molecular dynamics simulations

Abstract

SARS-CoV-2 is a positive-sense single-stranded RNA virus that causes a deadly coronavirus disease (COVID-19) in humans. The infection of SARS-CoV-2 in humans involves a viral surface spike glycoprotein containing the receptor-binding domain (RBD). The interactions of SARS-CoV-2 with the host angiotensin-converting enzyme 2 (ACE2) receptor are mediated by RBD. It binds to the host ACE2 and influences viral replication and disease pathogenesis. Therefore, targeting the RBD to prevent SARS-CoV-2 infections is of utmost importance. In this study, we used docking and molecular dynamics simulations to understand the binding effect of andrographolide on the SARS-CoV-2 spike protein. During docking, a strong binding affinity was observed between the ligand and the target receptor protein. MD results demonstrated higher conformational fluctuations in the ligand-free protein compared to the bound form. Several residues in the active sites make conformational rearrangements for the S protein to interact with the ligand. While RBD experiences conformational transition to gain more stability upon binding with the ligand. This binding is strengthened via several non-covalent interactions that make the complex structure more stable with higher binding affinity. Overall findings of the study may shed some valuable insights concerning the development of potential therapeutics in the strategies for COVID-19 prevention.

Ligand-binding induced conformational transition and stability of the receptor-binding domain of SARS-CoV-2 spike protein.

Communicated by Ramaswamy H. Sarma

Keywords:

• RBD
• S protein
• MD simulations
• protein–ligand complex
• binding energy

Acknowledgments

The authors thank the management of the Vellore Institute of Technology for providing the computational resources to complete this study.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

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