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

Antiviral Res. 2023 Oct 23:105737. doi: 10.1016/j.antiviral.2023.105737. Online ahead of print.ABSTRACTYellow 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 andin animal models.Anin 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 anEC50 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 i...
Source: Cell Research - Category: Cytology Authors: Source Type: research