Antiviral potential of black tea and blueberry extracts against monkeypox virus by targeting orthopoxvirus surface proteins.

Monkeypox virus (MPXV) outbreaks primarily affect resource-limited regions in Africa, highlighting an urgent need for low-cost, accessible therapeutics. Food-medicine homologous (FMH) substances, which are bioactive food components with medicinal properties, offer a promising therapeutic avenue owing to their low cost, favorable safety, and oral bioavailability. Here, we report that black tea extract (BTE) and blueberry extract (BBE), two representative FMH substances, can inhibit the vaccinia virus (VACV) and MPXV. Mechanistic studies suggest that BTE and BBE act at the post-attachment stage of viral entry by interacting with the orthopoxvirus surface proteins B6R and L1R. In a murine model of VACV infection, both extracts demonstrated modest in vivo antiviral efficacy. Furthermore, BTE and BBE exhibit in vitro synergistic antiviral activity when combined with each other or 3-hydroxypropionic acid-modified β-lactoglobulin (3HP-β-LG), a reported antiviral protein. These findings position BTE and BBE as promising, cost-effective candidates for further development as antivirals against MPXV in African regions.