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A selective histone deacetylase 6 inhibitor showed antiviral activity against dengue and zika viruses
Hao-Wen Shih1, Chang-Huei Tsao2, Yu-Hsiu Chang3, Chih-Wei Yang4, Shao-Wei Feng5, Kuo-Chou Chiu6
1 Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan
2 Department of Microbiology and Immunology, National Defense Medical Center; Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
3 Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
4 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
5 Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
6 Department of Family Dentistry, Tri-Service General Hospital, National Defense Medical Center; School of Dentistry, National Defense Medical Center, Taipei, Taiwan
Correspondence Address:
Kuo-Chou Chiu,
Department of Family Dentistry, Tri-Service General Hospital, No. 325. Section 2, Cheng Gong Road, Nei-Hu, Taipei 114
Taiwan
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/jmedsci.jmedsci_212_22
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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.
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