Title: In silico phytochemical repurposing of natural molecules as entry inhibitors against RBD of the spike protein of SARS-CoV-2 using molecular docking studies

Authors: Pawan Gupta; Swati Gupta; Sukrat Sinha; Shanthy Sundaram; Vishnu K. Sharma; Anjana Munshi

Addresses: Department of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandals Institute of Pharmacy, Dhule, Maharashtra-424001, India ' Centre of Biotechnology, University of Allahabad, Prayagraj, U.P-211002, India ' Department of Zoology, Nehru Gram Bharati (Deemed to be) University, Prayagraj-221505, India; Department of Zoology, Sri Venkateshwara College, University of Delhi, India ' Centre of Biotechnology, University of Allahabad, Prayagraj, U.P-211002, India ' Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab-160062, India ' Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, Punjab-151001, India

Abstract: The receptor binding domain (RBD) of Spike-protein (S-protein) is responsible for virus entry via interaction with host protein ACE2 (angiotensin-converting enzyme 2), present on the cell surface of humans. Therefore, S-protein is an important target to block the entry of the SARS-CoV-2 into the cell for further growth. In the present study, phytochemical repurposing of natural molecules: narirutin, naringin, neohesperidin and hesperidin were performed against the RBD S-protein/ACE2 interface as well as the RBD of the S-protein using molecular docking. These natural molecules were found to have structural similarity to each other and had binding potential against the viral infections. It is first time reported here that the naringin and narirutin are having binding potential against both RBD S-protein/ACE2 interface and active site of RBD of S-protein using binding mode analysis. Hence, this study will open avenues for multitargeting similar natural molecules binding against the SARS-CoV-2 proteins as all reports are made in this single study.

Keywords: SARS-CoV-2; spike protein; ACE2; natural molecules; binding mode analysis; docking.

DOI: 10.1504/IJCBDD.2023.130322

International Journal of Computational Biology and Drug Design, 2023 Vol.15 No.4, pp.267 - 288

Received: 23 Feb 2022
Accepted: 04 Jul 2022
Published online: 17 Apr 2023 *