JNJ4796 is an orally active fusion inhibitor of the influenza virus, inhibiting hemagglutinin (HA)-mediated fusion to neutralize the influenza A group 1 virus. JNJ4796 mimics the functionality of broadly neutralizing antibodies (bnAbs).

H1/Bris:(EC50)12 nM, H5/Viet:3.24 μM（EC50）, H1/Cal:66 nM(EC50), H1/PR8:22 nM(EC50), H1/SI06:13 nM（EC50）, H5/H97:449 nM（EC50）, H1/NCa:38 nM(EC50)

The mechanism of action of JNJ4796 is demonstrated to be based on inhibition of the pH-sensitive conformational change of HA, like bnAb CR6261. That triggers the fusion of the viral and endosomal membranes and the release of the viral genome into the host cell[1].

JNJ4796(50 and 10 mg/kg; twice daily) treatment, initiated one day before the challenge and continuing for 7 days, results in 100% survival at day 21 in comparison to the less potent compound JNJ8897 for which less than 50% survival is achieved. JNJ4796 (p.o.) protects mice from lethal challenge of 25 times the median lethal dose (LD50) of H1N1 A/Puerto Rico/8/1934 virus. Oral doses of JNJ4796 cause dose-dependent efficacy after a sublethal viral challenge (LD90), with twice-daily administration of 15 and 5 mg/kg of JNJ4796 giving rise to 100% survival[1].