Inhibition of Herpes Simplex Virus by Wedelolactone via Targeting Viral Envelope and Cellular TBK1/IRF3 and SOCS1/STAT3 pathways

Int J Antimicrob Agents. 2023 Oct 12:107000. doi: 10.1016/j.ijantimicag.2023.107000. Online ahead of print.ABSTRACTDevelopment of novel anti-herpes simplex virus (HSV) agents with active mechanisms different from nucleoside analogues is of high importance. Herein, we discovered that the natural coumarin compound wedelolactone (WDL) possessed inhibitory effects against both HSV-1 and HSV-2 in different cell lines with low toxicity, superior to the effects of acyclovir. WDL can directly inactivate the HSV particle via destruction of viral envelope, and block HSV replication process after virus adsorption, different from the mechanisms of acyclovir. Transcriptome analysis indicated that WDL may influence the host genes and signaling pathways related to HSV infection and immune responses. Further studies verified that WDL mainly interferes with the TBK1/IRF3 and SOCS1/STAT3 pathways to reduce HSV infection and inflammatory responses. Importantly, WDL treatment markedly improved mice survival, attenuated inflammatory symptoms, and reduced the virus titers in both HSV-1 and HSV-2 infected mice. Thus, the natural compound WDL has the potential to be developed into a novel anti-HSV agent targeting both viral envelope and cellular TBK1/IRF3 and SOCS1/STAT3 pathways.PMID:37838148 | DOI:10.1016/j.ijantimicag.2023.107000
Source: Herpes - Category: Infectious Diseases Authors: Source Type: research