Carbonization of citrus-derived flavonoids exhibits enhanced anti-coronavirus infection in vitro and in vivo.

Orange peel waste from juice processing has long been an environmental challenge. The abundant bioactive flavonoids, such as hesperidin and naringin, within the peel waste have attracted significant scientific interest. However, the low biocompatibility and the requirement for high effective concentrations to exert bioactivities hinder the capability and utility of these citrus-derived flavonoids. This study aimed to transform orange waste into a high-value product by enhancing the antiviral activity against coronavirus infection. The coronavirus pandemic, caused by SARS-CoV-2, has had a devastating impact on our quality of life and resulted in significant casualties. In this study, we modified and converted raw flavonoids into carbonized gel-like macromolecules and assessed their antiviral activity in cells infected with human coronavirus HCoV-229E. We found that hesperidin- and naringin-derived macromolecules exhibited greater anti-HCoV-229E effects and significantly reduced virus-induced cell death compared with raw flavonoids. These promising results from the in vitro model motivated the evaluation of flavonoid-macromolecule treatments in a mouse model of coronavirus infection, where they lessened weight loss and improved appearance and behavior. Our findings confirmed that novel antiviral candidates can be developed from resourceful agricultural plants and demonstrated that agricultural wastes, such as orange peels, can be further modified into biomedical products to diversify the available antimicrobial remedies. Overall, this work highlights a waste-to-value strategy for discovering urgently needed antiviral agents to bolster the resilience of our society against emerging and re-emerging coronavirus infections in the future.