Inhibition of poxvirus gene expression and genome replication by bisbenzimide derivatives

Research output: Contribution to journalArticle

Authors

  • Artur Yakimovich
  • Moona Huttunen
  • Benno Zehnder
  • Lesley J. Coulter
  • Victoria Gould
  • Christoph Schneider
  • Manfred Kopf
  • Colin J. McInnes
  • Urs F. Greber

Colleges, School and Institutes

External organisations

  • Universität Zürich
  • UCL
  • HPK H27
  • Moredun Research Institute
  • Institute of Biochemistry

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 antiviral 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 postreplicative 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.

Details

Original languageEnglish
Article numbere00838-17
JournalJournal of virology
Volume91
Issue number18
Early online date24 Aug 2017
Publication statusPublished - 1 Sep 2017

Keywords

  • Antiviral agents, DNA replication, Poxvirus, Vaccinia virus, Viral transcription