Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
Antiviral Res. 2020 Jun;178:104780. doi: 10.1016/j.antiviral.2020.104780. Epub 2020 Mar 27.
The ongoing threat of seasonal and pandemic influenza to human health requires antivirals that can effectively supplement existing vaccination strategies. The M2 protein of influenza A virus (IAV) is a proton-gated, proton-selective ion channel that is required for virus replication and is an established antiviral target. While licensed adamantane-based M2 antivirals have been historically used, M2 mutations that confer major adamantane resistance are now so prevalent in circulating virus strains that these drugs are no longer recommended. Here we review the current understanding of IAV M2 structure and function, mechanisms of inhibition, the rise of drug resistance mutations, and ongoing efforts to develop new antivirals that target resistant forms of M2.
季节性和大流行性流感对人类健康的持续威胁需要能够有效补充现有疫苗接种策略的抗病毒药物。流感 A 病毒 (IAV) 的 M2 蛋白是一种质子门控、质子选择性离子通道，是病毒复制所必需的，也是一个既定的抗病毒靶点。虽然历史上曾使用过许可的金刚烷类 M2 抗病毒药物，但现在循环病毒株中存在导致主要金刚烷类耐药的 M2 突变，以至于这些药物不再被推荐使用。在这里，我们回顾了对 IAV M2 结构和功能、抑制机制、耐药突变的出现以及正在努力开发针对耐药 M2 形式的新抗病毒药物的当前理解。
