Profiling the in vitro drug-resistance mechanism of influenza A viruses towards the AM2-S31N proton channel blockers.

ABSTRACT: The majority of human influenza A viruses currently in circulation carry the amantadine-resistant AM2-S31N channel mutation. We previously discovered a series of AM2-S31N inhibitors with potent antiviral activity against both oseltamivir-sensitive and -resistant influenza A viruses. To understand the drug-resistance mechanism of AM2-S31N inhibitors, we performed serial viral passage experiments using the influenza virus A/California/07/2009 (H1N1) to select drug-resistant AM2 mutations against two representative AM2-S31N channel blockers (1 and 2). Unlike amantadine, which gives rise to resistance after a single passage, compounds 1 and 2 selected for partially resistant viruses at passages 05 and 04 with a V27I and L26I mutation, respectively. This appears to suggest compounds 1 and 2 hav

SUBMITTER: Musharrafieh R 

PROVIDER: S-EPMC5891360 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature