2. Academic Validation
  3. Targeting Influenza A Virus RNA Promoter

Targeting Influenza A Virus RNA Promoter

  • Chem Biol Drug Des. 2015 Oct;86(4):663-73. doi: 10.1111/cbdd.12534.
Angel Bottini 1 2,  Surya K De 1,  Bainan Wu 1,  Changyan Tang 3,  Gabriele Varani 3,  Maurizio Pellecchia 1
Affiliations

Affiliations

  • 1 Infectious and Inflammatory Disease Center and Cancer Center, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
  • 2 Sanford Burnham Graduate School of Biomedical Sciences, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
  • 3 Department of Chemistry, University of Washington, Seattle, WA, 98195-1700, USA.
PMID: 25676805 DOI: 10.1111/cbdd.12534
Abstract

The emergence of drug-resistant strains of Influenza Virus makes exploring new classes of inhibitors that target universally conserved viral targets a highly important goal. The influenza A viral genome is made up of eight single-stranded RNA-negative segments. The RNA promoter, consisting of the conserved sequences at the 3' and 5' end of each RNA genomic segment, is universally conserved among influenza A virus strains and in all segments. Previously, we reported on the identification and NMR structure of DPQ (6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine) (compound 1) in complex with the RNA promoter. Here, we report on additional screening and SAR studies with compound 1, including ex vivo anti-influenza activity assays, resulted in improved cellular activity against influenza A virus in the micromolar range.

Keywords

chemical biology; drug design; drug discovery.

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