Vankadara Subramanyam, Dawson Monique Danielle, Fong Jia Yi, Oh Qin Yao, Ang Qi An, Liu Boping, Chang Hong Yun, Koh Judice, Koh Xiaoying, Tan Qian Wen, Joy Joma, Chia Cheng San Brian
Experimental Drug Development Centre, 10 Biopolis Road, Chromos #08-01, 138670 Singapore.
ACS Med Chem Lett. 2022 Jul 19;13(8):1345-1350. doi: 10.1021/acsmedchemlett.2c00260. eCollection 2022 Aug 11.
The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antiviral activities against human alphacoronavirus 229E was also investigated along with a cell-based assay. We discovered that the hydroxymethylketone and ketobenzothiazole warheads were equipotent to the nitrile warhead, suggesting that these analogs can also be used for treating coronavirus infections.
自2019年12月出现以来，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行目前正在造成一场前所未有的全球卫生紧急事件。2021年12月，美国食品药品监督管理局（FDA）批准了SARS-CoV-2主要蛋白酶抑制剂奈玛特韦紧急使用授权，用于治疗感染患者。这种拟肽类药物设计有一个腈基弹头，它与病毒蛋白酶形成共价键。在此，我们研究了具有不同弹头的奈玛特韦类似物及其抑制活性。此外，还通过基于细胞的试验研究了其对人α冠状病毒229E的抗病毒活性。我们发现，羟甲基酮和酮苯并噻唑弹头与腈基弹头具有同等效力，这表明这些类似物也可用于治疗冠状病毒感染。
