In-silico approaches for the screening and discovery of broad-spectrum marine natural product antiviral agents against coronaviruses

Boswell, Zachary and Verga, Jacopo Umberto and Mackle, James and Guerrero-Vazquez, Karen and Thomas, Olivier P. and Cray, James and Wolf, Bethany J. and Choo, Yeun Mun and Croot, Peter and Hamann, Mark and Hardiman, Gary (2023) In-silico approaches for the screening and discovery of broad-spectrum marine natural product antiviral agents against coronaviruses. Infection and Drug Resistance, 16. pp. 2321-2338. ISSN 1178-6973, DOI

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The urgent need for SARS-CoV-2 controls has led to a reassessment of approaches to identify and develop natural product inhibitors of zoonotic, highly virulent, and rapidly emerging viruses. There are yet no clinically approved broad-spectrum antivirals available for beta-coronaviruses. Discovery pipelines for pan-virus medications against a broad range of betacoronaviruses are therefore a priority. A variety of marine natural product (MNP) small molecules have shown inhibitory activity against viral species. Access to large data caches of small molecule structural information is vital to finding new pharmaceuticals. Increasingly, molecular docking simulations are being used to narrow the space of possibilities and generate drug leads. Combining in-silico methods, augmented by metaheuristic optimization and machine learning (ML) allows the generation of hits from within a virtual MNP library to narrow screens for novel targets against coronaviruses. In this review article, we explore current insights and techniques that can be leveraged to generate broad-spectrum antivirals against betacoronaviruses using in-silico optimization and ML. ML approaches are capable of simultaneously evaluating different features for predicting inhibitory activity. Many also provide a semi-quantitative measure of feature relevance and can guide in selecting a subset of features relevant for inhibition of SARS-CoV-2.

Item Type: Article
Funders: United States Department of Health & Human Services National Institutes of Health (NIH) - USA (Grant No: U54MD010706 & U01DA045300), QUB start-up funds
Uncontrolled Keywords: SARS-CoV-2; Natural products; Protease; Methyl transferases; RNA dependent polymerases; Viral transcription; Genome replication; Betacoronavirus
Subjects: Q Science > QR Microbiology > QR355 Virology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Ms Zaharah Ramly
Date Deposited: 30 Nov 2023 05:09
Last Modified: 30 Nov 2023 05:09

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