Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Adv Exp Med Biol. 2021;1322:285-312. doi: 10.1007/978-981-16-0267-2_11.
Nowadays, many viral infections have emerged and are taking a huge toll on human lives globally. Meanwhile, viral resistance to current drugs has drastically increased. Hence, there is a pressing need to design potent broad-spectrum antiviral agents to treat a variety of viral infections and overcome viral resistance. Covalent inhibitors have the potential to achieve both goals owing to their biochemical efficiency, prolonged duration of action, and the capability to inhibit shallow, solvent-exposed substrate-binding domains. In this chapter, we review the structures, activities, and inhibition mechanisms of covalent inhibitors against severe acute respiratory syndrome coronavirus 2, dengue virus, enterovirus, hepatitis C virus, human immunodeficiency virus, and influenza viruses. We also discuss the application of in silico study in covalent inhibitor design.
如今，许多病毒感染已经出现，并在全球范围内对人类生命造成了巨大的损失。同时，病毒对现有药物的耐药性也急剧增加。因此，迫切需要设计有效的广谱抗病毒药物来治疗各种病毒感染并克服病毒耐药性。由于共价抑制剂具有生化效率高、作用持续时间长以及能够抑制浅的、溶剂暴露的底物结合域的能力，因此有可能实现这两个目标。在本章中，我们综述了针对严重急性呼吸综合征冠状病毒 2、登革热病毒、肠病毒、丙型肝炎病毒、人类免疫缺陷病毒和流感病毒的共价抑制剂的结构、活性和抑制机制。我们还讨论了计算研究在共价抑制剂设计中的应用。
