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

Inhibition of Poxvirus Gene Expression and Genome Replication by Bisbenzimide Derivatives.

Yakimovich, A; Huttunen, M; Zehnder, B; Coulter, LJ; Gould, V; Schneider, C; Kopf, M; ... Mercer, J; + view all (2017) Inhibition of Poxvirus Gene Expression and Genome Replication by Bisbenzimide Derivatives. Journal of Virology , 91 (20) , Article e00838-17. 10.1128/JVI.00838-17. Green open access

[thumbnail of J. Virol.-2017-Yakimovich-JVI.00838-17.pdf]
Preview
Text
J. Virol.-2017-Yakimovich-JVI.00838-17.pdf - Accepted Version

Download (1MB) | Preview

Abstract

Virus infection of humans and livestock can be devastating for individuals and populations, sometimes resulting in large economic and societal impact. Prevention of virus disease by vaccination or anti-viral agents is difficult to achieve. A notable exception was the eradication of human smallpox by vaccination over 30 years ago. Today, humans and animals remain susceptible to poxvirus infections, including zoonotic poxvirus transmission. Here we identified a small molecule, bisbenzimide (bisbenzimidazole) and its derivatives, as potent agents against prototypic poxvirus infection in cell culture. We show that bisbenzimide derivatives, which preferentially bind the minor groove of double stranded DNA, inhibit vaccinia virus infection by blocking viral DNA replication and abrogating post-replicative intermediate and late gene transcription. The bisbenzimide derivatives are potent against vaccinia virus and other poxviruses but ineffective against a range of other DNA and RNA viruses. The bisbenzimide derivatives are the first inhibitors of-their-class, which appear to directly target the viral genome without affecting cell viability.IMPORTANCE Smallpox was one of the most devastating diseases in human history until it was eradicated by a worldwide vaccination campaign. Due to discontinuation of routine vaccination more than 30 years ago, the majority of today's human population remains susceptible to infection with poxviruses. Here we present a family of bisbenzimide (bisbenzimidazole) derivatives, known as Hoechst nuclear stains, with high potency against poxvirus infection. Results from a variety of assays used to dissect the poxvirus lifecycle demonstrate that bisbenzimides inhibit viral gene expression and genome replication. These findings can lead to the development of novel antiviral drugs that target viral genomes and blocking viral replication.

Type: Article
Title: Inhibition of Poxvirus Gene Expression and Genome Replication by Bisbenzimide Derivatives.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/JVI.00838-17
Publisher version: http://dx.doi.org/10.1128/JVI.00838-17
Language: English
Additional information: Copyright © 2017 Yakimovich et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
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
URI: https://discovery.ucl.ac.uk/id/eprint/1561221
Downloads since deposit
120Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item