Identification of camphor derivatives as novel M2 ion channel inhibitors of influenza A virus

Amantadine derivatives have been the only drugs marketed as M2 inhibitors of influenza A for decades. The identification of pinanamine as a novel M2 inhibitor suggests that M2 ion channels can accommodate more types of hydrophobic scaffolds. Herein, we further investigated the M2 ion channels and identified camphor derivatives as new types of M2 inhibitors. Compound 18 was found to be more potent than amantadine against wild-type influenza virus. The molecular docking revealed that compound 18 occupies more space in the M2 ion channel than amantadine and thus exhibits enhanced activity.