Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
Department of Biosciences & Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Simrol, Indore, 453552, India.
Antiviral Res. 2023 Mar;211:105555. doi: 10.1016/j.antiviral.2023.105555. Epub 2023 Feb 14.
Nirmatrelvir is the main component of Paxlovid, an oral antiviral drug approved for the treatment of COVID-19 caused by SARS-COV-2 infection. Nirmatrelvir targets the main protease (M), which is substantially conserved among different coronaviruses. Here, our molecular docking analysis indicates comparable affinity of nirmatrelvir binding to the M enzymes of SARS-CoV-2 and three seasonal coronaviruses (OC43, 229E and NL63). However, in cell culture models, we found that nirmatrelvir potently inhibited SARS-CoV-2, OC43 and 229E, but not NL63. The insensitivity of NL63 to nirmatrelvir treatment was demonstrated at both viral replication and infectious titer levels. The antiviral activity of nirmatrelvir against OC43 and 229E was further confirmed in human airway organoids. The combination of nirmatrelvir and molnupiravir exerted differential patterns of antiviral response against OC43 and 229E. These results revealed disparities in the ability of nirmatrelvir to inhibit different coronaviruses, and caution against repurposing of nirmatrelvir as a pan-coronavirus treatment.
尼马瑞韦是帕克洛维德的主要成分，帕克洛维德是一种口服抗病毒药物，已获批准用于治疗由 SARS-CoV-2 感染引起的 COVID-19。尼马瑞韦针对主要蛋白酶（M），不同的冠状病毒之间 M 高度保守。在这里，我们的分子对接分析表明，尼马瑞韦与 SARS-CoV-2 和三种季节性冠状病毒（OC43、229E 和 NL63）的 M 酶具有相当的亲和力。然而，在细胞培养模型中，我们发现尼马瑞韦能有效抑制 SARS-CoV-2、OC43 和 229E，但不能抑制 NL63。在病毒复制和感染滴度水平上，均证明 NL63 对尼马瑞韦治疗不敏感。尼马瑞韦对 OC43 和 229E 的抗病毒活性在人类气道类器官中得到进一步证实。尼马瑞韦和莫努匹拉韦的联合使用对 OC43 和 229E 表现出不同的抗病毒反应模式。这些结果揭示了尼马瑞韦抑制不同冠状病毒能力的差异，并提醒人们不要将尼马瑞韦重新用于泛冠状病毒治疗。
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