A new antiviral scaffold for human norovirus identified with computer-aided approaches on the viral polymerase

Giancotti, Gilda, Rigo, Ilaria, Pasqualetto, Gaia, Young, Mark T. ORCID: https://orcid.org/0000-0002-9615-9002, Neyts, Johan, Rocha-Pereira, Joana, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Ferla, Salvatore ORCID: https://orcid.org/0000-0002-5918-9237 and Bassetto, Marcella 2019. A new antiviral scaffold for human norovirus identified with computer-aided approaches on the viral polymerase. Scientific Reports 9 (1) , 18413. 10.1038/s41598-019-54903-7

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Abstract

Human norovirus is the leading cause of acute gastroenteritis worldwide, affecting every year 685 million people. In about one third of cases, this virus affects children under five years of age, causing each year up to 200,000 child deaths, mainly in the developing countries. Norovirus outbreaks are associated with very significant economic losses, with an estimated societal cost of 60 billion dollars per year. Despite the marked socio-economic consequences associated, no therapeutic options or vaccines are currently available to treat or prevent this infection. One promising target to identify new antiviral agents for norovirus is the viral polymerase, which has a pivotal role for the viral replication and lacks closely homologous structures in the host. Starting from the scaffold of a novel class of norovirus polymerase inhibitors recently discovered in our research group with a computer-aided method, different new chemical modifications were designed and carried out, with the aim to identify improved agents effective against norovirus replication in cell-based assays. While different new inhibitors of the viral polymerase were found, a further computer-aided ligand optimisation approach led to the identification of a new antiviral scaffold for norovirus, which inhibits human norovirus replication at low-micromolar concentrations.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences Pharmacy Biosciences
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License.
Publisher:	Nature Publishing Group
ISSN:	2045-2322
Date of First Compliant Deposit:	5 December 2019
Date of Acceptance:	20 November 2019
Last Modified:	06 Jan 2024 05:06
URI:	https://orca.cardiff.ac.uk/id/eprint/127353

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