Coronaviruses (CoVs) are responsible for a wide range of illnesses in both animals and human. The main protease (M) of CoVs is an attractive drug target, owing its critical and highly conserved role in viral replication. Here, we developed and refined an enzymatic technique to identify putative M inhibitors from 189 marine chemicals and 46 terrestrial natural products. The IC values of Polycarpine (), a marine natural substance we studied and synthesized, are 30.0 ± 2.5 nM for SARS-CoV-2 M and 0.12 ± 0.05 μM for PEDV M. Our research further demonstrated that pretreatment with Polycarpine () inhibited the betacoronavirus SARS-CoV-2 and alphacoronavirus PEDV multiplication in Vero-E6 cells. As a result, Polycarpine (), a pan-inhibitor of M, will function as an effective and promising antiviral option to combat CoVs infection and as a foundation for further therapeutic research.

中文翻译：

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一种源自海鞘的 Polycarpa aurata 的针对 Mpro 的冠状病毒泛抑制剂

冠状病毒 (CoV) 会导致动物和人类的多种疾病。冠状病毒的主要蛋白酶（M）是一个有吸引力的药物靶点，因为它在病毒复制中发挥着关键且高度保守的作用。在这里，我们开发并改进了一种酶技术，用于从 189 种海洋化学品和 46 种陆地天然产物中鉴定假定的 M 抑制剂。我们研究和合成的海洋天然物质 Polycarpine () 的 IC 值对于 SARS-CoV-2 M 为 30.0 ± 2.5 nM，对于 PEDV M 为 0.12 ± 0.05 μM。我们的研究进一步表明，Polycarpine () 预处理可抑制β 冠状病毒 SARS-CoV-2 和 α 冠状病毒 PEDV 在 Vero-E6 细胞中增殖。因此，Polycarpine（一种 M 的泛抑制剂）将作为一种有效且有前景的抗病毒药物来对抗 CoV 感染，并为进一步的治疗研究奠定基础。