Abstract：
The emergence of coronavirus disease 2019 (COVID-19), a novel identified pneumonia resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has significantly impacted and posed significant challenges to human society. The papain-like protease (PLpro) found in the nonstructural protein 3 of SARS-CoV-2 plays a vital role in viral replication. Moreover, PLpro disrupts the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 from host proteins. Consequently, PLpro has emerged as a promising drug target against SARS-CoV-2 infection. Computational studies have reported that ciclesonide can bind to SARS-CoV-2 PLpro. However, the inhibitory effects of ciclenoside on the PLpro have not been experimentally evaluated. Here, we evaluated the inhibitory effects of synthetic glucocorticoids (sGCs), including ciclesonide, on SARS-CoV-2 PLpro in vitro assay. Ciclesonide significantly inhibited the enzymatic activity of PLpro, compared with other sGCs and its IC50 was 18.4 ± 1.89 µM. These findings provide insights into the development of PLpro inhibitors.
摘要：
2019年冠状病毒病的出现（COVID-19），一种由严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）病毒引起的新型肺炎，对人类社会产生了重大影响并提出了重大挑战。SARS-CoV-2的非结构蛋白3中发现的木瓜蛋白酶（PLpro）在病毒复制中起着至关重要的作用。此外，PLpro通过从宿主蛋白切割泛素和干扰素刺激的基因15来破坏宿主免疫应答。因此,PLpro已成为对抗SARS-CoV-2感染的有希望的药物靶标。计算研究报道环索奈德可与SARS-CoV-2PLpro结合。然而,西来诺苷对PLpro的抑制作用尚未通过实验评估。这里,我们评估了合成糖皮质激素（sGCs）的抑制作用，包括环索奈德,SARS-CoV-2PLpro的体外检测。环索奈德显著抑制PLpro的酶活性，与其他sGC相比，其IC50为18.4±1.89µM。这些发现为PLpro抑制剂的开发提供了见解。
