Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry

Viruses
Michela MazzonMark Marsh

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 tha...Continue Reading

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Citations

Dec 13, 2019·Life Science Alliance·Camilla To BenfieldMark Marsh
Sep 29, 2019·F1000Research·Michela Mazzon, Mark Marsh
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Jun 18, 2020·Viruses·Aleksandr IanevskiDenis E Kainov
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Jul 3, 2021·International Journal of Molecular Sciences·Valeria De PasqualeLuigi Michele Pavone
Nov 2, 2021·Antimicrobial Agents and Chemotherapy·Jesse M YoungMichelle A Ozbun

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Datasets Mentioned

BETA
GM77

Methods Mentioned

BETA
Assay
transfection
flow cytometry
in vitro transcription
confocal microscopy
Infection

Software Mentioned

cellHTS2
GraphPad Prism
Excel
PE Columbus
Image
Stattic
FlowJo
Studio Lite

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