1. Targeting Influenza A Virus RNA Promoter.
- Author
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Bottini A, De SK, Wu B, Tang C, Varani G, and Pellecchia M
- Subjects
- Animals, Dogs, Drug Evaluation, Preclinical methods, Influenza A virus drug effects, Madin Darby Canine Kidney Cells drug effects, Madin Darby Canine Kidney Cells virology, Magnetic Resonance Spectroscopy, Molecular Structure, Peptide Library, Piperazines chemistry, Quinazolines chemistry, Structure-Activity Relationship, Virus Replication drug effects, Antiviral Agents chemistry, Antiviral Agents pharmacology, Influenza A virus genetics, Piperazines pharmacology, Promoter Regions, Genetic, Quinazolines pharmacology, RNA, Viral drug effects
- 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., (© 2015 John Wiley & Sons A/S.)
- Published
- 2015
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