Pimodivir is an inhibitor of influenza virus polymerase basic protein 2 (PB2; KD = <0.003 μM). It also binds to glycogen synthase kinase 3β (GSK3β; Ki = ~1.6 μM) and inhibits the activity of Axl and calcium/calmodulin-dependent protein kinase IIβ (CaMKIIβ) by greater than 50% in a panel of 65 human and rat kinases. Pimodivir decreases the replication of seven adamantine- and neuraminidase inhibitor-resistant strains of influenza virus A (EC50s = <0.15-2.8 nM in a cell-based assay). It increases the antiviral activity of oseltamivir , zanamivir , and favipiravir (T-705; ) with 50% combination index (CI50) values of 0.58, 0.64, and 0.89, respectively, in a cell-based assay. Pimodivir increases survival in a mouse model of intranasal influenza A infection when administered at doses of 1, 3, and 10 mg/kg twice per day.
