Focusing on the influenza virus polymerase complex: Recent progress in drug discovery and assay development

Jiantao Zhang, Yanmei Hu, Rami Musharrafieh, Hang Yin, Jun Wang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Influenza viruses are severe human pathogens that pose persistent threat to public health. Each year more people die of influenza virus infection than that of breast cancer. Due to the limited efficacy associated with current influenza vaccines, as well as emerging drug resistance from small molecule antiviral drugs, there is a clear need to develop new antivirals with novel mechanisms of action. The influenza virus polymerase complex has become a promising target for the development of the next-generation of antivirals for several reasons. Firstly, the influenza virus polymerase, which forms a heterotrimeric complex that consists of PA, PB1, and PB2 subunits, is highly conserved. Secondly, both individual polymerase subunit (PA, PB1, and PB2) and inter-subunit interactions (PA-PB1, PB1- PB2) represent promising drug targets. Lastly, growing insight into the structure and function of the polymerase complex has spearheaded the structure-guided design of new polymerase inhibitors. In this review, we highlight recent progress in drug discovery and assay development targeting the influenza virus polymerase complex and discuss their therapeutic potentials.

Original languageEnglish (US)
Pages (from-to)2243-2263
Number of pages21
JournalCurrent medicinal chemistry
Volume26
Issue number13
DOIs
StatePublished - 2019

Keywords

  • Influenza
  • PA
  • PB1
  • PB2
  • Polymerase
  • Ribonucleoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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