COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. The designed phosphate prodrug PF-07304814 is metabolized to PF-00835321 which is a potent inhibitor in vitro of the coronavirus family 3CL pro, with selectivity over human host protease targets. Furthermore, PF-00835231 exhibits potent in vitro antiviral activity against SARS-CoV-2 as a single agent and it is additive/synergistic in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of this compound as a potential COVID-19 treatment.

中文翻译：

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发现一种新型冠状病毒 3CL 蛋白酶抑制剂可用于 COVID-19 的潜在治疗

由 SARS-CoV-2 病毒引起的 COVID-19 已成为全球流行病。3CL 蛋白酶是一种病毒编码的蛋白质，在广泛的冠状病毒中是必不可少的，没有接近的人类类似物。设计的磷酸盐前药 PF-07304814在体外代谢为 PF-00835321，它是冠状病毒家族 3CL pro 的有效抑制剂，对人类宿主蛋白酶靶点具有选择性。此外，PF-00835231 作为单一药物表现出对 SARS-CoV-2 的有效体外抗病毒活性，并且与瑞德西韦组合具有相加/协同作用。我们提供了 ADME、安全性、体外和体内抗病毒活性数据，支持将该化合物作为一种潜在的 COVID-19 治疗进行临床评估。