UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry.

Mazzon, M; Ortega-Prieto, AM; Imrie, D; Luft, C; Hess, L; Czieso, S; Grove, J; ... Marsh, M; + view all (2019) Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry. Viruses , 11 (2) , Article 176. 10.3390/v11020176. Green open access

[thumbnail of Angel_Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry_VoR.pdf]
Preview
Text
Angel_Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry_VoR.pdf - Published Version

Download (2MB) | Preview

Abstract

Viruses are a major threat to human health and economic well-being. In recent years Ebola, Zika, influenza, and chikungunya virus epidemics have raised awareness that infections can spread rapidly before vaccines or specific antagonists can be made available. Broad-spectrum antivirals are drugs with the potential to inhibit infection by viruses from different groups or families, which may be deployed during outbreaks when specific diagnostics, vaccines or directly acting antivirals are not available. While pathogen-directed approaches are generally effective against a few closely related viruses, targeting cellular pathways used by multiple viral agents can have broad-spectrum efficacy. Virus entry, particularly clathrin-mediated endocytosis, constitutes an attractive target as it is used by many viruses. Using a phenotypic screening strategy where the inhibitory activity of small molecules was sequentially tested against different viruses, we identified 12 compounds with broad-spectrum activity, and found a subset blocking viral internalisation and/or fusion. Importantly, we show that compounds identified with this approach can reduce viral replication in a mouse model of Zika infection. This work provides proof of concept that it is possible to identify broad-spectrum inhibitors by iterative phenotypic screenings, and that inhibition of host-pathways critical for viral life cycles can be an effective antiviral strategy.

Type: Article
Title: Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry.
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/v11020176
Publisher version: https://doi.org/10.3390/v11020176
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0). https://creativecommons.org/licenses/by/4.0/
Keywords: broad-spectrum antivirals; host-targeted antivirals; alphaviruses; flaviviruses; endocytosis; virus entry; Zika; dengue; Semliki Forest virus; phenotypic screening
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > VP: Health
UCL > Provost and Vice Provost Offices > VP: Health > Translational Research Office
URI: https://discovery.ucl.ac.uk/id/eprint/10069179
Downloads since deposit
55Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item