Auraptene Has Antiviral Activity against Human Coronavirus OC43 in MRC-5 Cells

Auraptene (7-geranyloxycoumarin) is the abundant prenyloxycoumarin found in the fruits of Citrus spp. Auraptene has a variety of pharmacological and therapeutic functions, such as anticancer, antioxidant, immunomodulatory, and anti-inflammation activities, with excellent safety profiles. In this study, we evaluated the anticoronaviral activity of auraptene in HCoV-OC43-infected human lung fibroblast MRC-5 cells. We found that auraptene effectively inhibited HCoV-OC43-induced cytopathic effects with 4.3 μM IC₅₀ and 6.1 μM IC₉₀, resulting in a selectivity index (CC₅₀/IC₅₀) of >3.5. Auraptene treatment also decreased viral RNA levels in HCoV-OC43-infected cells, as detected through quantitative real-time PCR, and decreased the expression level of spike proteins and nucleocapsid proteins in virus-infected cells, as detected through the Western blot analysis and immunofluorescence staining. Time-of-addition analysis showed auraptene's inhibitory effects at the post-entry stage of the virus life cycle; however, auraptene did not induce the antiviral interferon families, IFN-α1, IFN-β1, and IFN-λ1. Additionally, auraptene-treated MRC-5 cells during HCoV-OC43 infection decreased the MMP-9 mRNA levels which are usually increased due to the infection, as auraptene is a previously reported MMP-9 inhibitor. Therefore, auraptene showed antiviral activity against HCoV-OC43 infection, and we suggest that auraptene has the potential to serve as a therapeutic agent against human coronavirus.