Inhibitory effect of [6]-shogaol against 3CLpro activity and SARS-CoV-2 infection

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BACKGROUND: Zingiber officinale Roscoe (ginger) has been traditionally used not only as a culinary ingredient, but also for its medicinal properties. In Japan, ginger-derived crude drugs are categorized into dried ginger (Zingiberis Rhizoma [ZR]) or steamed ginger (Zingiberis Rhizoma processum [ZR-P]). Heating ginger converts gingerol, the primary component of ZR, into shogaol. In this study, we aimed to evaluate the inhibitory effects of ginger and its constituents on SARS-CoV-2 infection. METHODS: We assessed the inhibitory effects of ZR, ZR-P, [6]-gingerol, and [6]-shogaol on SARS-CoV-2 infection in VeroE6/TMPRSS2 cells. To understand the molecular mechanism underlying this inhibitory effect, we evaluated the activity of [6]-shogaol against the viral proteases 3 C-like protease (3CLpro) and papain-like protease (PLpro). RESULTS: We observed that ZR-P (66.1% suppression at 50 µg/ml) and [6]-shogaol (70.0% suppression at 25 µM) exhibited significant inhibitory effects against SARS-CoV-2 infection. We found that [6]-shogaol effectively inhibited 3CLpro activities both in vitro (20.4% inhibition at 40 µM) and in FlipGFP reporter system (19.7% inhibition at 25 µM). CONCLUSIONS: This study highlights [6]-shogaol and ZR-P as promising natural inhibitors of SARS-CoV-2, providing new insights into the pharmacological potential of traditional ginger preparations and their active components against COVID-19.

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