Sirihongthong Thanyaporn, Jitobaom Kunlakanya, Boonarkart Chompunuch, Thongon Songkran, Auewarakul Prasert
Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
J Med Virol. 2025 Jul;97(7):e70488. doi: 10.1002/jmv.70488.
Emerging and important endemic viral diseases without effective antiviral are important public health threat. An effective broad-spectrum antiviral can be a pivotal tool to mitigate future epidemics and provide a solution for endemic viral diseases. Molnupiravir, a pyrimidine analog, is known for the COVID-19 treatment. It has been shown to inhibit a broad range of RNA viruses. Inhibition of de novo pyrimidine synthesis by teriflunomide, a dihydroorotate dehydrogenase inhibitor, also showed potent antiviral activity against various RNA viruses. Mechanistically, pyrimidine synthesis inhibition should enhance the activity of molnupiravir as it reduces competition of native nucleotides to incorporate into nascent viral RNA. Molnupiravir and teriflunomide combination has been recently shown to have synergistic effect against SARS-CoV-2. Here we show that the combination of β-D-N4-hydroxycytidine, the active form of molnupiravir, and teriflunomide also showed synergistic activity against many RNA viruses. This combination may offer an effective antiviral regimen not only for future emerging viral diseases but also existing important viral diseases.
缺乏有效抗病毒药物的新出现且重要的地方性病毒疾病是重大的公共卫生威胁。一种有效的广谱抗病毒药物可能是减轻未来疫情并为地方性病毒疾病提供解决方案的关键工具。莫努匹拉韦是一种嘧啶类似物，以用于治疗新冠病毒病而闻名。它已被证明能抑制多种RNA病毒。二氢乳清酸脱氢酶抑制剂特立氟胺对从头嘧啶合成的抑制作用，也显示出对多种RNA病毒具有强大的抗病毒活性。从机制上讲，嘧啶合成抑制应会增强莫努匹拉韦的活性，因为它减少了天然核苷酸掺入新生病毒RNA的竞争。莫努匹拉韦和特立氟胺联合用药最近已显示出对严重急性呼吸综合征冠状病毒2具有协同作用。在此我们表明，莫努匹拉韦的活性形式β-D-N4-羟基胞苷与特立氟胺的联合用药对许多RNA病毒也显示出协同活性。这种联合用药不仅可能为未来新出现的病毒疾病，也为现有的重要病毒疾病提供一种有效的抗病毒治疗方案。
