Stanford University has received a USD 1.27 million NIAID R56 grant to advance a novel oral small molecule antiviral against influenza A virus (IAV) toward an investigational new drug (IND) application, targeting a mechanism distinct from all approved influenza therapies.
The lead compound, STF-8562, inhibits the amphipathic helix (AH) motif of the IAV M2 protein — a target not addressed by oseltamivir (Tamiflu), baloxavir, or amantadine. In a mouse lethal-challenge model, the compound the researchers term an M2AH inhibitor provided 100% protection even when administered three days post-infection, a timepoint at which oseltamivir and baloxavir the grant states are ineffective. Two lead series appear to target distinct aspects of the M2AH motif and demonstrate synergistic activity against each other, potentially enabling combination dosing. The program's stated goals include once-daily oral dosing, IND-enabling toxicology in rats and dogs, and assembly of a full IND package for human clinical testing.
The existing antiviral arsenal for IAV remains limited, with currently recommended drugs targeting either viral neuraminidase or the cap-dependent endonuclease. Adamantanes including amantadine are no longer recommended in the US because of widespread resistance among circulating influenza A viruses. STF-8562's reported activity against IAV resistant to oseltamivir, baloxavir, and amantadine, combined with its distinct M2 AH target, could therefore provide a complementary mechanism for both seasonal influenza treatment and pandemic preparedness.