期刊
ANTIVIRAL RESEARCH
卷 207, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2022.105400
关键词
Dengue virus; Sulforaphane; Heme oxygenase-1; Interferon
资金
- Ministry of Science and Technology of Taiwan [MOST110-2314-B-037-117-MY2, MOST111-2311-B-110-001, NSYSYKMU 111-I06]
- NSYSU-KMU Joint Research Project
- [MOST107-2311-B-037-005-MY3]
Dengue virus (DENV) infection is a life-threatening disease with no effective treatment options. However, a study found that sulforaphane (SFN) has significant antiviral activity against DENV by inducing heme oxygenase-1 (HO-1) expression and inhibiting viral protease activity. This suggests that SFN could be a promising candidate for treating DENV.
Dengue virus (DENV) infection is a life-threatening disease that causes severe dengue hemorrhagic fever and dengue shock syndrome. There is currently no effective therapeutic agent or widely used vaccine for treating DENV infections. In this study, sulforaphane (SFN), an antioxidant phytocompound, exhibited significant anti-viral activity, with a half-inhibitory concentration value of 5.8 +/- 0.7 mu M to suppress viral RNA replication. Mechanistic studies demonstrated that SFN-induced heme oxygenase-1 (HO-1) expression, which inhibited viral protease activity, leading to the restoration of antiviral interferon (IFN) responses against DENV replication. Its antiviral activity can be attenuated by the knockdown of HO-1 expression by short hairpin RNA and blockage of activity with a specific inhibitor, supporting the contention that HO-1 induction contributes to the anti-DENV activity of SFN. SFN also stimulated HO-1 induction through an Nrf2-dependent pathway. SFN effectively prolonged the survival rate and reduced the virus titer in DENV-infected ICR suckling mice with activated expression of interferon-stimulated genes. The anti-DENV activity of SFN was also observed in the IFN-deficient AG129 mouse model. Collectively, SFN represents significant anti-DENV activity in vitro and in vivo and is a promising drug candidate or dietary supplement against DENV.
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