School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; ; Department of Physiology, Huaihua Medical College, Huaihua 418000, China.
J Thorac Dis. 2013 Aug;5 Suppl 2(Suppl 2):S149-59. doi: 10.3978/j.issn.2072-1439.2013.06.14.
Influenza virus has caused seasonal epidemics and worldwide pandemics, which caused tremendous loss of human lives and socioeconomics. Nowadays, only two classes of anti-influenza drugs, M2 ion channel inhibitors and neuraminidase inhibitors respectively, are used for prophylaxis and treatment of influenza virus infection. Unfortunately, influenza virus strains resistant to one or all of those drugs emerge frequently. Hemagglutinin (HA), the glycoprotein in influenza virus envelope, plays a critical role in viral binding, fusion and entry processes. Therefore, HA is a promising target for developing anti-influenza drugs, which block the initial entry step of viral life cycle. Here we reviewed recent understanding of conformational changes of HA in protein folding and fusion processes, and the discovery of HA-based influenza entry inhibitors, which may provide more choices for preventing and controlling potential pandemics caused by multi-resistant influenza viruses.
流感病毒已造成季节性流行和全球性大流行，给人类生命和社会经济带来了巨大损失。目前，仅有 M2 离子通道抑制剂和神经氨酸酶抑制剂两类抗流感病毒药物用于流感病毒感染的预防和治疗。遗憾的是，流感病毒株对这些药物中的一种或全部经常产生耐药性。血凝素（HA）是流感病毒包膜上的糖蛋白，在病毒结合、融合和进入过程中发挥关键作用。因此，HA 是开发抗流感药物的一个有前途的靶点，这些药物可以阻断病毒生命周期的初始进入步骤。本文综述了近年来对 HA 在蛋白折叠和融合过程中构象变化的认识，以及基于 HA 的流感进入抑制剂的发现，这可能为预防和控制由多耐药流感病毒引起的潜在大流行提供更多选择。
