Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, People's Republic of China.
Antiviral Res. 2012 Nov;96(2):91-9. doi: 10.1016/j.antiviral.2012.09.001. Epub 2012 Sep 13.
The 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 S31NM2 than amantadine. This study provides a new insight into the structural nature of drugs required to inhibit WT A/M2 and its mutants.
金刚烷胺类是一类抗流感药物，可抑制甲型流感病毒的 M2 离子通道。然而，最近由于出现了对金刚烷胺不敏感的 A/M2 突变体，这些药物的临床效果受到了质疑。我们之前曾报道过(1R,2R,3R,5S)-3-莰烷胺 3 是一种新型的野生型流感 A 病毒 M2 蛋白（WT A/M2）抑制剂，但对金刚烷胺耐药的 M2 突变体的抑制作用有限。在这项研究中，我们探讨了新合成的莰烷胺衍生物是否能够抑制 WT A/M2 并选择对金刚烷胺耐药的 M2 突变体。发现几种莰烷胺的咪唑和胍唑衍生物对 WT A/M2 的抑制作用与金刚烷胺相当，其中一种化合物 12 对 A/M2-S31N 突变体有较弱的抑制作用，对 S31NM2 的抑制作用比金刚烷胺略强。这项研究为抑制 WT A/M2 及其突变体所需的药物的结构性质提供了新的见解。
