Naesens Lieve, Stevaert Annelies, Vanderlinden Evelien
Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
Curr Opin Pharmacol. 2016 Oct;30:106-115. doi: 10.1016/j.coph.2016.08.003. Epub 2016 Aug 26.
Adequate response to severe influenza infections or pandemic outbreaks requires two complementary strategies: preventive vaccination and antiviral therapy. The existing influenza drugs, M2 blockers and neuraminidase inhibitors, show modest clinical efficacy and established or potential resistance. In the past three years, several new agents have entered the clinical pipeline and already yielded some promising data from Phase 2 trials. For two main categories, that is, the broadly neutralizing anti-hemagglutinin antibodies and small-molecule inhibitors of the viral polymerase complex, crystallography was instrumental to guide drug development. These structural insights also aid to expand the activity spectrum towards influenza A plus B viruses, or conceive nucleoprotein or polymerase assembly inhibitors. The practice of influenza therapy should radically change in the next decade.
预防性疫苗接种和抗病毒治疗。现有的流感药物,即M2阻滞剂和神经氨酸酶抑制剂,临床疗效一般,且存在已确定的或潜在的耐药性。在过去三年中,几种新型药物已进入临床试验阶段,并且已经从2期试验中获得了一些有前景的数据。对于两个主要类别,即广泛中和抗血凝素抗体和病毒聚合酶复合物的小分子抑制剂,晶体学在指导药物开发方面发挥了重要作用。这些结构上的见解也有助于扩大对甲型和乙型流感病毒的活性谱,或构思核蛋白或聚合酶组装抑制剂。未来十年,流感治疗的实践将发生根本性变化。