泛素样蛋白ISG15抗冠状病毒感染作用的研究进展  

Progress on the research of anti-infection role of ubiquitin-like protein ISG15 against coronavirus

作　　者：刘欣然[1] 陈桐 张煜[1] 陈红[1] LIU Xinran;CHEN Tong;ZHANG Yu;CHEN Hong(School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan430030,China)

机构地区：[1]华中科技大学同济医学院药学院,武汉430030

出　　处：《华中师范大学学报（自然科学版）》2023年第5期748-757,共10页Journal of Central China Normal University：Natural Sciences

基　　金：国家自然科学基金项目(81973360).

摘　　要：干扰素刺激基因15(ISG15,interferon-stimulated gene 15)是一种泛素样蛋白,在调节机体天然免疫和抗病毒感染过程中发挥重要作用。ISG15在针对流感病毒、乙型肝炎病毒、HIV病毒、埃博拉病毒、SARS病毒、中东呼吸综合征冠状病毒、巨细胞病毒等病毒的抗病毒研究已有文献报道。除此以外,最新的研究表明ISG15分子会在新型冠状病毒的木瓜蛋白酶样蛋白酶的作用下失活,从而抑制其抗病毒功能。因此抑制新型冠状病毒木瓜蛋白酶样蛋白酶,除能直接阻断病毒的生命周期、抑制病毒在体内的复制以外,同时也会提升ISG15分子水平,继而间接提升机体免疫能力,降低感染风险。该文介绍ISG15抗新冠病毒的过程,重点介绍ISG15抗冠状病毒作用的特异性,此外,总结新冠病毒通过木瓜蛋白酶样蛋白酶阻断ISG15介导的天然免疫实现免疫逃避的机制,并罗列了潜在的木瓜蛋白酶样蛋白酶的抑制剂。本文从ISG15抗病毒天然免疫的分子机制角度,总结抗SARS-CoV-2药物的最新进展,并对相关药物的研发前景进行展望。The ISG15 molecule is a ubiquitin-like protein that plays an important role in regulating innate immunity against viral infection.Previous studies have reported the antiviral mechanisms of ISG15 against viral infection,such as influenza virus,hepatitis B virus,HIV virus,Ebola virus,SARS-CoV,MERS-CoV and cytomegalovirus.Recently,a number of studies reported the function of ISG15 in SARS-CoV-2 infection,that ISG15 can be inactivated by the papain-like protease of SARS-CoV-2,thereby inhibiting its antiviral function.In this review,we presented the antiviral mechanism of ISG15,emphasizing the specificity of the antiviral effects of ISG15 against coronaviruses.Moreover,the immune evasion ability of coronavirus via papain-like protease(PLpro)by blocking ISG15-dominated innate immunity,as well as the potential therapeutic inhibitors of PLpro were also reviewed.From the perspective of the molecular mechanism of ISG15's antiviral innate immunity,the latest progress of anti-SARS-CoV-2 drugs was summarized,as well as0x09 the prospect of the related drug research and development.

关 键 词：泛素样蛋白ISG15 ISG15修饰 木瓜蛋白酶样蛋白酶 冠状病毒 

分 类 号：R373[医药卫生—病原生物学]