Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Department of Applied Biological Science, Tokyo University of Science, Noda 278-8510, Japan.
Viruses. 2022 Apr 6;14(4):764. doi: 10.3390/v14040764.
Current anti-hepatitis B virus (HBV) drugs are suppressive but not curative for HBV infection, so there is considerable demand for the development of new anti-HBV agents. In this study, we found that fungus-derived exophillic acid inhibits HBV infection with a 50% maximal inhibitory concentration (IC50) of 1.1 µM and a 50% cytotoxic concentration (CC50) of >30 µM in primary human hepatocytes. Exophillic acid inhibited preS1-mediated viral attachment to cells but did not affect intracellular HBV replication. Exophillic acid appears to target the host cells to reduce their susceptibility to viral attachment rather than acting on the viral particles. We found that exophillic acid interacted with the HBV receptor, sodium taurocholate cotransporting polypeptide (NTCP). Exophillic acid impaired the uptake of bile acid, the original function of NTCP. Consistent with our hypothesis that it affects NTCP, exophillic acid inhibited infection with HBV and hepatitis D virus (HDV), but not that of hepatitis C virus. Moreover, exophillic acid showed a pan-genotypic anti-HBV effect. We thus identified the anti-HBV/HDV activity of exophillic acid and revealed its mode of action. Exophillic acid is expected to be a potential new lead compound for the development of antiviral agents.
目前的抗乙型肝炎病毒 (HBV) 药物仅对 HBV 感染具有抑制作用，而不能治愈 HBV 感染，因此人们对开发新型抗 HBV 药物有很大的需求。在这项研究中，我们发现真菌来源的外生酸以 1.1 µM 的 50%最大抑制浓度 (IC50) 和 30 µM 以上的 50%细胞毒性浓度 (CC50) 抑制 HBV 感染。外生酸抑制 preS1 介导的病毒与细胞的附着，但不影响细胞内 HBV 复制。外生酸似乎靶向宿主细胞以降低其对病毒附着的易感性，而不是作用于病毒颗粒。我们发现外生酸与 HBV 受体，牛磺胆酸钠共转运蛋白 (NTCP) 相互作用。外生酸损害了 NTCP 的原始功能，即胆汁酸的摄取。外生酸与我们的假设一致，即它影响 NTCP，因此抑制 HBV 和丁型肝炎病毒 (HDV) 的感染，但不抑制丙型肝炎病毒的感染。此外，外生酸显示出泛基因型抗 HBV 作用。因此，我们确定了外生酸的抗 HBV/HDV 活性，并揭示了其作用机制。外生酸有望成为开发抗病毒药物的潜在新先导化合物。
