RT Journal Article
T1 Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry.
A1 Mazzon, Michela
A1 Ortega-Prieto, Ana María
A1 Imrie, Douglas
A1 Luft, Christin
A1 Hess, Lena
A1 Czieso, Stephanie
A1 Grove, Joe
A1 Skelton, Jessica Katy
A1 Farleigh, Laura
A1 Bugert, Joachim
A1 Wright, Edward
A1 Temperton, Nigel
A1 Angell, Richard
A1 Oxenford, Sally
A1 Jacobs, Michael
A1 Ketteler, Robin
A1 Dorner, Marcus
A1 Marsh, Mark
K1 Antivirales
AB 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.
PB MDPI
YR 2019
FD 2019
LK https://hdl.handle.net/10630/35587
UL https://hdl.handle.net/10630/35587
LA eng
NO Mazzon, M.; Ortega-Prieto, A.M.; Imrie, D.; Luft, C.; Hess, L.; Czieso, S.; Grove, J.; Skelton, J.K.; Farleigh, L.; Bugert, J.J.; et al. Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry. Viruses 2019, 11, 176. https://doi.org/10.3390/v11020176
NO M.M. (Michela Mazzon) and M.M. (Mark Marsh) are supported by UK Medical Research Councilfunding to the MRC-UCL LMCB University Unit (MC_UU_12018/1), and from UCL Confidence in Conceptand Therapeutic Innovation Fund awards. M.D. was supported by a Wellcome Trust New Investigator award(104771/Z/14/Z), a starting grant from the European Research Council (ERC-StG-2015-637304), and fundingthrough the Imperial NIHR Biomedical Research Centre.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026