A Selective Histone Deacetylase 6 Inhibitor Showed Antiviral Activity Against Dengue and Zika Viruses

Background: Flavivirus comprises several important viruses, including dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV). A large outbreak of DENV and ZIKV occurred in these years, leading to many cases of illness and death. However, despite the decades of efforts, there a...

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Published inJournal of Medical Sciences Vol. 43; no. 5; pp. 219 - 226
Main Authors Shih, Hao-Wen, Tsao, Chang-Huei, Chang, Yu-Hsiu, Yang, Chih-Wei, Feng, Shao-Wei, Chiu, Kuo-Chou
Format Journal Article
LanguageEnglish
Published 國防醫學院 01.09.2023
Wolters Kluwer India Pvt. Ltd
Medknow Publications and Media Pvt. Ltd
Wolters Kluwer Medknow Publications
Subjects
anti-viral drugs
Antiviral agents
dengue virus
flavivirus
histone deacetylase 6 inhibitors
Vorinostat
zika virus
Japan
histone deacetylase 6 inhibitors
Zika virus
Flavivirus
dengue virus
anti‑viral drugs
anti-viral drugs
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Summary:Background: Flavivirus comprises several important viruses, including dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV). A large outbreak of DENV and ZIKV occurred in these years, leading to many cases of illness and death. However, despite the decades of efforts, there are no specific therapeutic drugs against DENV and ZIKV. Several studies had shown that histone deacetylase 6 inhibitors (HDAC6 inhibitors) possess antiviral effects on influenza A virus, hepatitis C virus, and JEV. Aim: The purpose of this study is to examine the antiviral effect of the compound J34803, a newly synthesized HDAC6 inhibitor, against DENV and ZIKV in vitro and in vivo. Methods: We investigated whether the compound J34803 inhibited viral infection by western blot and virus titer determination. The signaling pathway of inhibition was also determined by western blot. Results: The compound J34803 exhibited superior antiviral activities against DENV‑2, DENV‑4, and ZIKV compared to Tubastatin A (TBSA), and its antiviral mechanism may through suppressing HDAC6 and its downstream signaling pathway. Moreover, treatment with the compound J34803 could reduce viremia levels in DENV‑2‑and ZIKV‑infected AG129 mice. Conclusion: We demonstrated that the compound J34803 had better therapeutic efficacy in virus infection as compared to TBSA and could be a potential potent therapeutic drug against emerging flaviviral infections.
ISSN:1011-4564
DOI:10.4103/jmedsci.jmedsci_212_22