蛋白类病毒感染失活剂:“遇敌即杀”的利器

Protein-based virus inactivators: immediate inactivators of circulating virions

由包膜病毒,例如人类免疫缺陷病毒(human immunodeficiency virus, HIV)及严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)等引发的传染病,对人类健康和全球公共卫生造成了很大的威胁.目前已有的抗病毒药物大多数通过作用于病毒入侵细胞时或进入细胞后的生活周期来抑制感染.这些药物在遇到游离的病毒时,并不能导致病毒失去感染性,而是等待病毒感染细胞后发挥抑制作用.蛋白类病毒感染失活剂是一类可直接作用于游离病毒并导致其失去感染性的抗病毒蛋白或多肽,其主要通过与病毒颗粒上包膜蛋白(envelope glycoproteins, Envs)中的一个或多个位点相互作用,引发病毒包膜蛋白功能丧失或病毒基因组释放等,从而使病毒失去感染性.值得注意的是,蛋白类病毒感染失活剂有望比传统的抗病毒药物具有更高的利用率,且在体内应用时比化学类失活剂更安全,因此越来越受到关注.本文选择一些研究较多的代表性病毒,重点介绍了HIV, SARS-CoV及SARS-CoV-2,登革病毒(dengue virus, DENV)及寨卡病毒(Zika virus, ZIKV)的蛋白类病毒感染失活剂研究的最新进展,以及其用于紧急应对新发和再现病毒大暴发、大流行的潜力.

Infectious diseases caused by enveloped viruses, such as human immunodeficiency virus(HIV) and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), pose significant threats to global public health. Most currently available antiviral drugs inhibit viral infection by inhibiting the viral entry process or intracellular viral replications. However, these agents have little antiviral effect while in circulation and instead exert their inhibitory activity during or after virions infect cells. In contrast, protein-based virus inactivators are antiviral proteins or peptides able to directly inactivate free virions. Virus inactivators primarily function by interacting with one or more sites on virion envelope glycoproteins(Envs), causing Env impairment or viral genome release. Proteinbased virus inactivators have attracted increasing attention as they are expected to have a higher utilization rate than current antiviral drugs and be safer for in vivo human applications than chemical-based virus inactivators. Herein, we summarize recent progress in developing protein-based virus inactivators against several important enveloped viruses, including HIV, SARS-CoV and SARS-CoV-2, dengue virus(DENV), and Zika virus(ZIKV). Further, we discuss their potential uses during outbreaks or pandemics caused by emerging or re-emerging viruses.