An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19
An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19
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DOI：
10.1126/science.abl4784
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发表时间：
2021-12-24
期刊：
影响因子：
56.9
通讯作者：
Zhu, Yuao
中科院分区：
文献类型：
--
作者：
Owen, Dafydd R.;Allerton, Charlotte M. N.;Zhu, Yuao
由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的COVID-19全球爆发已成为全球大流行。除疫苗外，抗病毒治疗是应对COVID-19持续威胁的医疗保健应对措施的重要组成部分。在这里，我们报告了PF-07321332的发现和表征，PF-07321332是一种口服生物可利用的SARS-CoV-2主要蛋白酶抑制剂，具有体外泛人类冠状病毒抗病毒活性和优异的脱靶选择性和体内安全性。PF-07321332已在小鼠适应性SARS-CoV-2模型中证明了口服活性，并在健康人类受试者的I期临床试验中达到了超过体外抗病毒细胞效价的口服血浆浓度。
The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to countering the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency in a phase 1 clinical trial in healthy human participants.