BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Viral RNA polymerase PA subunit; viral RNA polymerase PB1 subunit

May 7, 2015 7:00 AM UTC

In vitro studies suggest inhibitors of interactions between influenza viral RNA polymerase PA and PB1 subunits could help treat influenza infection. Chemical synthesis and in vitro testing of triazolopyrimidine analogs identified a lead compound that inhibited the interaction between the two subunits with an IC50 of 1 μM, inhibited influenza A RNA polymerase activity comparably to generic ribavirin (EC50 values 12 and 18 μM, respectively) and had low cytotoxicity in human cells (IC50 >250 μM). In human cells infected with various influenza A and B strains, including an oseltamivir-resistant clinical isolate, the lead compound inhibited plaque formation - a measure of viral-induced cell killing - with EC50 values of 7-25 μM. Next steps could include testing the lead compound in animal models of influenza infection.

The generic nucleoside analog ribavirin, a broad-spectrum inhibitor of viral RNA polymerases, is marketed to treat hepatitis C virus (HCV) and other viral infections...