Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2023-10-20 , DOI: 10.1016/j.bmcl.2023.129530 Daniels Jelisejevs 1 , Anna Lina Bula 1 , Linda Kinena 1
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The main protease (Mpro) of SARS-CoV-2 is an attractive drug target for COVID-19 treatment as it plays an integral role in the proliferation of coronavirus. Herein, we describe the investigation of β- and γ-lactams as electrophilic “warheads” for covalent binding to Cys145 of the Mpro active site. The highest inhibitory activity (IC50 = 45 ± 3 μM) was achieved using a pyrazolidinone warhead attached to the targeting dipeptide. Importantly, the synergy of the warhead and the targeting dipeptide is crucial for the successful inhibition of Mpro.
中文翻译：
基于吡唑烷酮的拟肽 SARS-CoV-2 Mpro 抑制剂
SARS-CoV-2 的主要蛋白酶 （Mpro） 是 COVID-19 治疗的有吸引力的药物靶点，因为它在冠状病毒的增殖中起着不可或缺的作用。在本文中，我们描述了 β-和 γ-内酰胺作为与 Mpro 活性位点的 Cys145 共价结合的亲电“弹头”的研究。使用连接到靶向二肽的吡唑烷酮弹头获得最高抑制活性 （IC50 = 45 ± 3 μM）。重要的是，弹头和靶向二肽的协同作用对于成功抑制 Mpro 至关重要。
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