Antiviral Mechanisms and Preclinical Evaluation of Amantadine Analogs that Continue to Inhibit Influenza A Viruses with M2^S31N-Based Drug Resistance

To better manage seasonal and pandemic influenza infections, new drugs are needed with enhanced activity against amantadine- and rimantadine-resistant influenza A virus (IAV) strains containing the S31N variant of the viral M2 ion channel (M2^(S31N)). Here we tested 36 amantadine analogs against a panel of viruses containing either M2^(S31N) or the parental, M2 S31 wild-type variant (M2^(WT)). We found that several analogs, primarily those with sizeable lipophilic adducts, inhibited up to …