【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。更多还原

【Abstract】 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 as the prospect of the related drug research and development.更多还原