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Targeting Influenza A Virus RNA Promoter
Author(s) -
Bottini Angel,
De Surya K.,
Wu Bainan,
Tang Changyan,
Varani Gabriele,
Pellecchia Maurizio
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12534
Subject(s) - rna , virus , influenza a virus , virology , biology , genome , gene , rna virus , genetics
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.