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(E)-Guggulsterone Inhibits Dengue Virus Replication by Upregulating Antiviral Interferon Responses through the Induction of Heme Oxygenase-1 Expression by Chen, Wei-Chun (author);Wei, Chih-Ku (author);Hossen, Monir (author);Hsu, Yao-Chin (author);Lee, Jin-Ching (author) is a Medicine article available to read on EtoBox.

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Dengue virus (DENV) infection, which causes dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is a severe global health problem in tropical and subtropical areas. There is no effective vaccine or drug against DENV infection. Thus, the development of anti-DENV agents is imperative. This study aimed to assess the anti-DENV activity of (E)-guggulsterone using a DENV infectious system. A specific inhibitor targeting signal molecules was used to evaluate the molecular mechanisms of action. Western blotting and qRT-PCR were used to determine DENV protein expression and RNA replication, respectively. Finally, an ICR suckling mouse model was used to examine the anti-DENV activity of (E)-guggulsterone in vivo. A dose-dependent inhibitory effect of (E)-guggulsterone on DENV protein synthesis and RNA replication without cytotoxicity was observed. The mechanistic studied revealed that (E)-guggulsterone stimulates Nrf2-mediated heme oxygenase-1 (HO-1) expression, which increases the antiviral interferon responses and downstream antiviral gene expression by blocking DENV NS2B/3B protease activity. Moreover, (E)-guggulsterone protected ICR suckling mice from life-threatening DENV

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Author

Chen, Wei-Chun (author);Wei, Chih-Ku (author);Hossen, Monir (author);Hsu, Yao-Chin (author);Lee, Jin-Ching (author)

Publisher

MDPI AG

Published

2021

Language

EN

Field

Medicine (Health Sciences)