Sulforaphane suppresses dengue virus replication by inhibition of dengue protease and enhancement of antiviral interferon response. - GreenMedInfo Summary
Sulforaphane suppresses dengue virus replication by inhibition of dengue protease and enhancement of antiviral interferon response through Nrf2-mediated heme oxygenase-1 induction.
Antiviral Res. 2022 Aug 31 ;207:105400. Epub 2022 Aug 31. PMID: 36055433
Wei-Chun Chen
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 antiviral activity, with a half-inhibitory concentration value of 5.8 ± 0.7 μM 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 beattenuated 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.