Hooda Preeti, Al-Dosari Mohammed, Sinha Neha, Parvez Mohammad K, Sehgal Deepak
Virology Lab, Department of Life Sciences, Shiv Nadar Institute of Eminence, Gautam Budh Nagar 201314, India.
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
ACS Omega. 2023 Oct 27;8(44):41570-41578. doi: 10.1021/acsomega.3c05637. eCollection 2023 Nov 7.
Hepatitis E virus (HEV) is primarily a hepatotropic virus that is responsible for acute hepatitis E in the general population and for chronic hepatitis in immunocompromised individuals. In the absence of a globally accessible vaccine, pegylated interferon-α and ribavirin are the only antiviral agents available for the treatment of chronic patients. As viral RNA-dependent RNA polymerases (RdRps) are indispensable for RNA replication, they are considered potential drug targets. In this study, we screened some well-known RdRp inhibitor molecules, notably, favipiravir, sofosbuvir, remdesivir, filibuvir, and tegobuvir. Of these, monotherapy with favipiravir and sofosbuvir inhibited the RdRp activity with an IC value of 10.2 ± 4.9 and 5.2 ± 2.9 μM, respectively, compared to the reference drug ribavirin (3.5 ± 1.6 μM). Further investigation of the combination therapy showed a reduction in viral RNA copy numbers by approximately 90%. Therefore, favipiravir has an additive effect when used with sofosbuvir. Therefore, we propose that favipiravir is a promising anti-HEV drug that can be used in combination with sofosbuvir.
戊型肝炎病毒（HEV）主要是一种嗜肝病毒，可导致普通人群发生急性戊型肝炎，以及免疫功能低下个体发生慢性肝炎。在全球范围内尚无可用疫苗的情况下，聚乙二醇化干扰素-α和利巴韦林是仅有的可用于治疗慢性患者的抗病毒药物。由于病毒RNA依赖性RNA聚合酶（RdRps）对于RNA复制不可或缺，因此它们被视为潜在的药物靶点。在本研究中，我们筛选了一些知名的RdRp抑制剂分子，特别是法匹拉韦、索磷布韦、瑞德西韦、替比夫定和替诺福韦酯。其中，与参考药物利巴韦林（3.5±1.6μM）相比，法匹拉韦和索磷布韦单药治疗分别以10.2±4.9和5.2±2.9μM的IC值抑制了RdRp活性。联合治疗的进一步研究表明，病毒RNA拷贝数减少了约90%。因此，法匹拉韦与索磷布韦联用时具有相加作用。因此，我们认为法匹拉韦是一种有前景的抗HEV药物，可与索磷布韦联合使用。
