Zhao, XinJie, YanlingRosenberg, MatthewWan, JuntingZeng, ShaogaoCui, WeiXiao, YipingLi, ZhiyuanTu, ZhengchaoCasarotto, MarcoHu, Wenhui2015-12-100166-3542http://hdl.handle.net/1885/55038The adamantanes are a class of anti-influenza drugs that inhibit the M2 ion channel of the influenza A virus. However recently, the clinical effectiveness of these drugs has been called into question due to the emergence of adamantane-insensitive A/M2 mutants. Although we previously reported (1R,2R,3R,5S)-3-pinanamine 3 as a novel inhibitor of the wild type influenza A virus M2 protein (WT A/M2), limited inhibition was found for adamantane-resistant M2 mutants. In this study, we explored whether newly synthesized pinanamine derivatives were capable of inhibiting WT A/M2 and selected adamantane-resistant M2 mutants. Several imidazole and guanazole derivatives of pinanamine were found to inhibit WT A/M2 to a comparable degree as amantadine and one of these compounds 12 exhibits weak inhibition of A/M2-S31N mutant and it is marginally more effective in inhibiting S31N. M2 than amantadine. This study provides a new insight into the structural nature of drugs required to inhibit WT A/M2 and its mutants.Keywords: adamantane; amantadine; antivirus agent; bl 1743; guanazole; imidazole derivative; pinanamine derivative; protein M2; rimantadine; unclassified drug; article; drug design; drug structure; drug synthesis; Influenza virus A; mutant; priority journal; wild t Influenza A virus; M2 ion channel; Pinanamine derivatives201210.1016/j.antiviral.2012.09.0012016-02-24