Researchers from various institutions have collaborated to investigate the potential of Citrus depressa Hayata, a traditional Chinese medicinal herb, in inhibiting different variants of the SARS-CoV-2 virus. Citrus depressa has a long history of use in traditional Taiwanese medicine for treating respiratory ailments. This study aims to isolate universal inhibitors from Citrus depressa that specifically target the SARS-CoV-2 spike protein and elucidate the mechanisms behind their inhibitory effects.
Using advanced techniques such as surface plasmon resonance (SPR) assays, SARS-CoV-2 pseudo-virus assays, molecular docking, and ELISA-based spike protein binding assays, the researchers extracted the whole fruit of Citrus depressa and derived various fractions to explore its inhibitory potential. The study found that both the crude extract and the ethyl acetate layer of Citrus depressa exhibited notable inhibitory activity against the SARS-CoV-2 variant Omicron BA.4/5. Polymethoxyflavones (PMFs), compounds found in Citrus depressa, emerged as potent inhibitors of the spike protein, disrupting its interaction with hACE2.
Further analysis revealed the mechanisms of action of the identified compounds, with molecular docking analyses providing insights into their binding affinity and interactions with specific amino acid residues within the spike protein and hACE2 complex. Cd3 and Cd8, two compounds isolated from Citrus depressa, exhibited a strong affinity for the spike protein, disrupting its interaction with hACE2. The study also compared the bioactivities of these compounds with NRICM101, a traditional Chinese medicine prescription known for its positive therapeutic outcomes against SARS-CoV-2, and found notable anti-SARS-CoV-2 activity.
The focus on Citrus depressa aligns with the principles of traditional Chinese medicine, where the herb has been historically used to treat various ailments. The rich content of polymethoxyflavonoids in Citrus depressa suggests its potential in downregulating key signaling pathways and mitigating the severity of infections. This study not only validates the traditional use of Citrus depressa but also establishes its potential as a therapeutic agent against SARS-CoV-2.
In conclusion, this comprehensive study has uncovered the inhibitory effect of polymethoxyflavones from Citrus depressa on the SARS-CoV-2 spike protein. The crude extract and specific compounds, especially Cd3 and Cd8, have shown significant potential in preventing infections from different SARS-CoV-2 variants. As the world continues to combat the challenges posed by the COVID-19 pandemic, this research opens avenues for innovative approaches to antiviral drug development. Natural products, particularly those rooted in traditional medicine, offer a promising reservoir for potential therapeutic agents. This study not only contributes to our understanding of Citrus depressa’s therapeutic potential but also emphasizes the importance of exploring nature’s bounty in the search for effective antiviral treatments.