SARS-CoV-2 has emerged as a world public health threat. Herein, we report that the clinical approved auranofin could perfectly inhibit the activity of 3-chymotrypsin-like cysteine protease (Mpro or 3CLpro) of SARS-CoV-2. Gold cluster could significantly inhibit 3CLpro of SARS-COV-2. Phenyl isothiocyanate and Vitamin K3 could well suppress the activity of 3CLpro. For Mpro inhibition, IC50 of auranofin, Vitamin K3, phenyl isothiocyanate, gold cluster are about 0.51 micromolar/L, 7.96 micromolar/L, 10.13 micromolar/L, 1.61 micromolar/L, respectively. These compounds may be with potentials for treatment SARS-CoV-2 virus replication. Especially for FDA approved auranofin, it is an anti-inflammation drug in clinic, thus it may with strong potential to inhibit virus replication and suppress the inflammation damage in COVID-19 patients. Gold cluster is with better safety index and well anti-inflammation in vitro/vivo, therefore it is with potential to inhibit virus replication and suppress the inflammation damage caused by COVID-19 virus. As Au(I) ion is active metabolism specie derived from gold compounds or gold clusters in vivo, further computational studies revealed Au ion could tightly bind thiol group of Cys145 residue of 3CLpro thus inhibit enzyme activity. Also, phenyl isothiocyanate and Vitamin K3 may interact with thiol group of Cys145 via Michael addition reaction, molecular dynamic (MD) theory studied are applied to confirmed these small molecules are stable in the pocket and inhibit Mpro activity.

中文翻译：

---

分子抑制SARS-CoV-2病毒3-胰凝乳蛋白酶样半胱氨酸蛋白酶的酶活性：实验和理论研究

SARS-CoV-2已成为世界公共卫生威胁。在此，我们报道临床批准的金诺芬可以完全抑制SARS-CoV-2的3-胰凝乳蛋白酶样半胱氨酸蛋白酶（Mpro或3CLpro）的活性。金簇可以显着抑制SARS-COV-2的3CLpro。苯基异硫氰酸酯和维生素K3可以很好地抑制3CLpro的活性。对于Mpro抑制，金诺芬，维生素K 3，异硫氰酸苯酯，金簇的IC 50分别为约0.51微摩尔/L、7.96微摩尔/L、10.13微摩尔/L、1.61微摩尔/ L。这些化合物可能具有治疗SARS-CoV-2病毒复制的潜力。特别是对于FDA批准的金诺芬，它在临床上是一种抗炎药，因此在抑制病毒复制和抑制COVID-19患者的炎症损害方面可能具有很强的潜力。金簇具有更好的安全指数和良好的体外/体内抗炎性，因此具有抑制病毒复制和抑制由COVID-19病毒引起的炎症损害的潜力。由于Au（I）离子是体内衍生自金化合物或金簇的活性代谢物质，因此进一步的计算研究表明Au离子可以紧密结合3CLpro的Cys145残基的巯基，从而抑制酶的活性。此外，异硫氰酸苯酯和维生素K3可能通过Michael加成反应与Cys145的巯基相互作用，应用分子动力学（MD）理论来证实这些小分子在口袋中稳定并抑制Mpro活性。因此，它具有抑制病毒复制和抑制由COVID-19病毒引起的炎症损害的潜力。由于Au（I）离子是体内衍生自金化合物或金簇的活性代谢物质，因此进一步的计算研究表明Au离子可以紧密结合3CLpro的Cys145残基的巯基，从而抑制酶的活性。此外，异硫氰酸苯酯和维生素K3可能通过Michael加成反应与Cys145的巯基相互作用，应用分子动力学（MD）理论来证实这些小分子在口袋中稳定并抑制Mpro活性。因此，它具有抑制病毒复制和抑制由COVID-19病毒引起的炎症损害的潜力。由于Au（I）离子是体内衍生自金化合物或金簇的活性代谢物质，因此进一步的计算研究表明Au离子可以紧密结合3CLpro的Cys145残基的巯基，从而抑制酶的活性。此外，异硫氰酸苯酯和维生素K3可能通过Michael加成反应与Cys145的巯基相互作用，应用分子动力学（MD）理论来证实这些小分子在口袋中稳定并抑制Mpro活性。