An In Silico Design of Peptides Targeting the S1/S2 Cleavage Site of the SARS-CoV-2 Spike Protein

Chian Ho and Wan Fahmi Wan Mohamad Nazarie and Lee, Ping Chin (2023) An In Silico Design of Peptides Targeting the S1/S2 Cleavage Site of the SARS-CoV-2 Spike Protein. Viruses, 15. pp. 1-27. ISSN 1999-4915

	Text ABSTRACT.pdf Download (45kB)
	Text FULL TEXT.pdf Restricted to Registered users only Download (10MB)

Abstract

SARS-CoV-2, responsible for the COVID-19 pandemic, invades host cells via its spike protein, which includes critical binding regions, such as the receptor-binding domain (RBD), the S1/S2 cleavage site, the S2 cleavage site, and heptad-repeat (HR) sections. Peptides targeting the RBD and HR1 inhibit binding to host ACE2 receptors and the formation of the fusion core. Other peptides target proteases, such as TMPRSS2 and cathepsin L, to prevent the cleavage of the S protein. However, research has largely ignored peptides targeting the S1/S2 cleavage site. In this study, bioinformatics was used to investigate the binding of the S1/S2 cleavage site to host proteases, including furin, trypsin, TMPRSS2, matriptase, cathepsin B, and cathepsin L. Peptides targeting the S1/S2 site were designed by identifying binding residues. Peptides were docked to the S1/S2 site using HADDOCK (High-Ambiguity-Driven protein–protein DOCKing). Nine peptides with the lowest HADDOCK scores and strong binding affinities were selected, which was followed by molecular dynamics simulations (MDSs) for further investigation. Among these peptides, BR582 and BR599 stand out. They exhibited relatively high interaction energies with the S protein at −1004.769 ± 21.2 kJ/mol and −1040.334 ± 24.1 kJ/mol, respectively. It is noteworthy that the binding of these peptides to the S protein remained stable during the MDSs. In conclusion, this research highlights the potential of peptides targeting the S1/S2 cleavage site as a means to prevent SARS-CoV-2 from entering cells, and contributes to the development of therapeutic interventions against COVID-19.

Item Type:	Article
Keyword:	SARS-CoV-2, S1/S2 cleavage site, Peptides, HADDOCK, molecular dynamics simulation
Subjects:	R Medicine > RA Public aspects of medicine > RA1-1270 Public aspects of medicine > RA421-790.95 Public health. Hygiene. Preventive medicine > RA643-645 Disease (Communicable and noninfectious) and public health
Department:	FACULTY > Faculty of Science and Natural Resources
Depositing User:	SITI AZIZAH BINTI IDRIS -
Date Deposited:	29 Nov 2023 10:35
Last Modified:	29 Nov 2023 10:35
URI:	https://eprints.ums.edu.my/id/eprint/37729

Actions (login required)

View Item