Zhang Luping, Zhou Dengyuan, Li Qiuyan, Zhu Shuo, Imran Muhammad, Duan Hongyu, Cao Shengbo, Ke Shaoyong, Ye Jing
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Front Microbiol. 2021 Oct 6;12:727236. doi: 10.3389/fmicb.2021.727236. eCollection 2021.
Flaviviruses are the major emerging arthropod-borne pathogens globally. However, there is still no practical anti-flavivirus approach. Therefore, existing and emerging flaviviruses desperately need active broad-spectrum drugs. In the present study, the antiviral effect of steroidal dehydroepiandrosterone (DHEA) and 23 synthetic derivatives against flaviviruses such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), and Dengue virus (DENV) were appraised by examining the characteristics of virus infection both and . Our results revealed that AV1003, AV1004 and AV1017 were the most potent inhibitors of flavivirus propagation in cells. They mainly suppress the viral infection in the post-invasion stage in a dose-dependent manner. Furthermore, orally administered compound AV1004 protected mice from lethal JEV infection by increasing the survival rate and reducing the viral load in the brain of infected mice. These results indicate that the compound AV1004 might be a potential therapeutic drug against JEV infection. These DHEA derivatives may provide lead scaffolds for further design and synthesis of potential anti-flavivirus potential drugs.
黄病毒是全球主要的新兴节肢动物传播病原体。然而，目前仍没有实用的抗黄病毒方法。因此，现有的和新出现的黄病毒迫切需要有效的广谱药物。在本研究中，通过检测病毒感染的特征，评估了甾体脱氢表雄酮（DHEA）及其23种合成衍生物对日本脑炎病毒（JEV）、寨卡病毒（ZIKV）和登革病毒（DENV）等黄病毒的抗病毒作用。我们的结果显示，AV1003、AV1004和AV1017是细胞中黄病毒繁殖最有效的抑制剂。它们主要以剂量依赖的方式在入侵后阶段抑制病毒感染。此外，口服化合物AV1004通过提高存活率和降低感染小鼠脑中的病毒载量，保护小鼠免受致死性JEV感染。这些结果表明，化合物AV1004可能是一种潜在的抗JEV感染治疗药物。这些DHEA衍生物可能为进一步设计和合成潜在的抗黄病毒药物提供先导支架。
