2. Academic Validation
  3. Tiratricol inhibits yellow fever virus replication through targeting viral RNA-dependent RNA polymerase of NS5

Tiratricol inhibits yellow fever virus replication through targeting viral RNA-dependent RNA polymerase of NS5

  • Antiviral Res. 2023 Nov:219:105737. doi: 10.1016/j.antiviral.2023.105737.
Hao Ren 1,  Jiaqi Wang 1,  Hailin Tang 1,  Xijing Qian 1,  Binghui Xia 1,  Zhenghan Luo 1,  Zhenghao Xu 1,  Zhongtian Qi 2,  Ping Zhao 3
Affiliations

Affiliations

  • 1 Department of Microbiology, Faculty of Naval Medicine, Shanghai Key Laboratory of Medical Biodefense, Naval Medical University, Shanghai, China.
  • 2 Department of Microbiology, Faculty of Naval Medicine, Shanghai Key Laboratory of Medical Biodefense, Naval Medical University, Shanghai, China. Electronic address: [email protected].
  • 3 Department of Microbiology, Faculty of Naval Medicine, Shanghai Key Laboratory of Medical Biodefense, Naval Medical University, Shanghai, China. Electronic address: [email protected].
PMID: 37879570 DOI: 10.1016/j.antiviral.2023.105737
Abstract

Yellow fever virus (YFV) Infection is a major public concern that threatens a large population in South America and Africa. No specific Antiviral drugs are available for treating yellow fever. Here, we report that tiratricol (triiodothyroacetic acid, TRIAC), a clinically approved drug used to treat thyroid hormone resistance syndrome (THRS), is a potent YFV inhibitor both in host cells and in animal models.An in vitro study demonstrates that TRIAC remarkably suppresses viral RNA synthesis and protein expression in a dose-dependent manner in human hepatoma cell lines (Huh-7) with an EC50 value of 2.07 μM and a CC50 value of 385.77 μM respectively. The surface plasmon resonance assay and molecular docking analysis indicate that TRIAC hinders viral replication by binding to the RNA-dependent RNA polymerase (RdRp) domain of viral nonstructural protein NS5, probably through interacting with the active sites of RdRp.The inhibitory effect of TRIAC in vivo is also confirmed in 3-week old C57BL/6 mice challenged with YFV Infection, from which the survival of the mice as well as lesions and Infection in their tissues and serum issignificantly promoted following oral administration of TRIAC (0.2 mg/kg/day). Additionally, TRIAC shows a broad-spectrum Antiviral activity against multiple flaviviruses such as TBEV, WNV,ZIKV, andJEV in vitro. Our data demonstrate that the TH analogue TRIAC is an effective anti-YFV compound and may act as a potential therapeutic candidate for the treatment of YFV Infection if its clinical importance is determined in patients in future.

Keywords

Antiviral drug; NS5; Tiratricol; Viral replication; Yellow fever virus.

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