Coronaviruses (CoVs) are a large family of respiratory viruses which can cause mild to moderate upper respiratory tract infections. Recently, new coronavirus named as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified which is a major threat to public health. Innate immune responses play a vital role in a host's defence against viruses. Interestingly, CoVs have evolved elaborate strategies to evade the complex system of sensors and signalling molecules to suppress host immunity. SARS-CoV-2 papain-like protease (PLpro), as an important coronavirus enzyme, regulates viral spread and innate immune responses. SCoV-2 PLpro is multifunctional enzyme with deubiquitinating (DUB) and deISGylating activity. The PLpro can interact with key regulators in signalling pathways such as STING, NF-κB, cytokine production, MAPK and TGF-β and hijack those to block the immune responses. Therefore, the PLpro can be as an important target for the treatment of COVID-19. Until now, several drugs or compounds have been identified that can inhibit PLpro activity. Here we discuss about the dysregulation effects of PLpro on immune system and drugs that have potential inhibitors for SCoV-2 PLpro.

中文翻译：

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SARS 冠状病毒 2 类木瓜蛋白酶与免疫系统之间的相互作用：治疗 COVID-19 的潜在药物靶点

冠状病毒 (CoV) 是一大类呼吸道病毒，可引起轻度至中度上呼吸道感染。最近，一种名为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的新型冠状病毒被发现，它对公众健康构成重大威胁。先天免疫反应在宿主防御病毒方面起着至关重要的作用。有趣的是，冠状病毒已经进化出复杂的策略来逃避复杂的传感器和信号分子系统来抑制宿主免疫。SARS-CoV-2 类木瓜蛋白酶 (PLpro) 作为一种重要的冠状病毒酶，可调节病毒传播和先天免疫反应。SCoV-2 PLpro 是具有去泛素化 (DUB) 和去 ISG 活性的多功能酶。PLpro 可以与信号通路中的关键调节剂相互作用，例如 STING、NF-κB、细胞因子产生、MAPK 和 TGF-β 并劫持它们以阻断免疫反应。因此，PLpro 可以作为治疗 COVID-19 的重要靶点。到目前为止，已经确定了几种可以抑制 PLpro 活性的药物或化合物。在这里，我们讨论了 PLpro 对免疫系统的失调影响以及具有 SCoV-2 PLpro 潜在抑制剂的药物。