Disrupting SARS-CoV-2 spike protein activity: a virtual screening and binding assay study

Queirós-Reis, Luís, Alvites, Rui, Maurício, Ana Colette, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Bassetto, Marcella and Mesquita, João R. 2024. Disrupting SARS-CoV-2 spike protein activity: a virtual screening and binding assay study. International Journal of Molecular Sciences 26 (1) , p. 151. 10.3390/ijms26010151

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Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that emerged in late 2019 and rapidly spread worldwide, causing the COVID-19 pandemic. The spike glycoprotein (S protein) plays a crucial role in viral target recognition and entry by interacting with angiotensin, converting enzyme 2 (ACE2), the functional receptor for the virus, via its receptor binding domain (RBD). The RBD availability for this interaction can be influenced by external factors, such as fatty acids. Linoleic acid (LA), a free fatty acid, has been shown to bind the S protein, modulating the viral infection by reducing initial target recognition. LA interacts with the fatty acid binding pocket (FABP), a potential drug target against SARS-CoV-2. In this study, we aimed to exploit the FABP as a drug target by performing a docking-based virtual screening with a library of commercially available, drug-like compounds. The virtual hits identified were then assessed in in vitro assays for the inhibition of the virus–host interaction and cytotoxicity. Binding assays targeting the spike–ACE2 interaction identified multiple compounds with inhibitory activity and low cytotoxicity.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Pharmacy
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Start Date: 2024-12-27
Publisher:	MDPI
ISSN:	1661-6596
Date of First Compliant Deposit:	6 January 2025
Date of Acceptance:	21 December 2024
Last Modified:	06 Jan 2025 12:30
URI:	https://orca.cardiff.ac.uk/id/eprint/175024

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