The Antiviral Effect of Novel Steroidal Derivatives on Flaviviruses

Luping Zhang; Dengyuan Zhou; Qiuyan Li; Shuo Zhu; Muhammad Imran; Hongyu Duan; Shengbo Cao; Shaoyong Ke; Jing Ye

doi:10.3389/fmicb.2021.727236

The Antiviral Effect of Novel Steroidal Derivatives on Flaviviruses

Front Microbiol. 2021 Oct 6:12:727236. doi: 10.3389/fmicb.2021.727236. eCollection 2021.

Authors

Luping Zhang^{1

2

3}, Dengyuan Zhou^{1

2

3}, Qiuyan Li^{1

2

3}, Shuo Zhu^{1

2

3}, Muhammad Imran^{1

2

3}, Hongyu Duan^{1

2

3}, Shengbo Cao^{1

2

3}, Shaoyong Ke⁴, Jing Ye^{1

2

3}

Affiliations

¹ State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
² Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
³ The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China.
⁴ National Biopesticide Engineering Research Center, Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, China.

Abstract

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 in vitro and in vivo. 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.

Keywords: DHEA derivatives; antiviral activity; flavivirus; steroids; therapy.