Dengvaxia^® (CTD‐TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD‐TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti‐HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS‐461203) was predicted to bind to the catalytic motif (Gly‐Asp‐Asp) of dengue viral polymerase with binding affinity of −6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC₉₀ of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS‐461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in‐depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue.

中文翻译：

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Sofosbuvir可以预防登革热吗？

Dengvaxia ^®（CTD-TDV）是赛诺菲巴斯德（Sanofi Pasteur）唯一获得许可的四价登革热疫苗，自2015年以来上市。但是，总体而言，CTD-TDV的管理尚未收到世界卫生组织的资格预审建议。因此，具有通用的抗登革热剂进行治疗将是有益的。因此，许多人已经研究了干扰登革热感染的对登革热病毒聚合酶特异的核苷抑制剂的开发。另外，我们使用了市售的抗HCV前药索非布韦来研究其抗登革热的计算机和体外作用。结果，据推测索非布韦的活性代谢产物（GS-461203）以-6.9 kcal / mol的结合亲和力与登革热病毒聚合酶的催化基序（Gly-Asp-Asp）结合。此外，₉₀ 0.4μ米。此外，这项研究表明需要特殊的肝酶来激活前药进入GS-461203，以发挥其抗登革热的潜力。总而言之，应该对索非布韦进行深入研究，以提供其对登革热的功效及其在人类受试者中作为DENV聚合酶抑制剂的潜在潜力的信息。总之，我们已经扩大了临床可用药物索非布韦作为登革热治疗的潜力。