Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Department of Microbiology, Kanagawa Prefectural Institute of Public Health, Kanagawa, Japan.
Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan.
Antiviral Res. 2019 May;165:42-46. doi: 10.1016/j.antiviral.2019.03.002. Epub 2019 Mar 7.
Dengue virus (DENV) is the most prevalent human arthropod-borne virus and causes severe problems worldwide, mainly in tropical and sub-tropical regions. However, there is no specific antiviral drug against DENV infection. We and others recently reported that stearoyl-CoA desaturase-1 (SCD1) inhibitor showed potent suppression of hepatitis C virus replication. In this study, we examined the impact of SCD1 on DENV replication. We found that SCD1 inhibitors (MK8245 and #1716) dramatically suppressed DENV replication in a dose-dependent manner without cytotoxicity. This anti-DENV efficacy was observed against all four DENV serotypes and other flaviviruses, including Zika virus and Japanese encephalitis virus. A subgenomic replicon system of DENV was used to confirm that SCD1 inhibitor suppressed viral RNA replication. Interestingly, exogenous supplementation of unsaturated fatty acids resulted in recovery of the DENV titer even in the presence of SCD1 inhibitor, suggesting that fatty acid biosynthesis contributes to DENV genome replication. These findings indicate that SCD1 is a novel host factor required for DENV replication, and SCD1 inhibitor is a potential candidate for treating dengue fever.
登革热病毒（DENV）是最常见的人类节肢动物传播病毒，在全球范围内造成严重问题，主要在热带和亚热带地区。然而，目前还没有针对 DENV 感染的特定抗病毒药物。我们和其他人最近报道称，硬脂酰辅酶 A 去饱和酶-1（SCD1）抑制剂对丙型肝炎病毒复制具有强大的抑制作用。在这项研究中，我们研究了 SCD1 对 DENV 复制的影响。我们发现 SCD1 抑制剂（MK8245 和 #1716）以剂量依赖的方式显著抑制 DENV 复制，而没有细胞毒性。这种抗 DENV 功效在所有四种 DENV 血清型和其他黄病毒（包括寨卡病毒和日本脑炎病毒）中均观察到。使用 DENV 的亚基因组复制子系统证实 SCD1 抑制剂抑制病毒 RNA 复制。有趣的是，即使存在 SCD1 抑制剂，不饱和脂肪酸的外源补充也导致 DENV 滴度恢复，表明脂肪酸生物合成有助于 DENV 基因组复制。这些发现表明 SCD1 是 DENV 复制所必需的新型宿主因子，SCD1 抑制剂是治疗登革热的潜在候选药物。
