Utilizing natural compounds as ligands to disrupt the binding of SARS-CoV-2 receptor-binding domain to angiotensin-converting enzyme 2, impeding viral infection
Jingyi Wu, Ting-Hsu Chen, Zi-Han Shen, May-Jywan Tsai, Max K Leong, Yan-Qiang Huang, Ching-Feng Weng
Phytochemistry Letters, doi:10.1016/j.phytol.2025.102999
Currently, no specific antiviral drug has been definitively proven effective in treating patients with severe coronavirus disease 2019 . Various specific strategies have been employed against COVID-19; however, several potent antiviral candidates, including prodrugs and repurposed drugs, are still under urgent investigation, particularly in the search for molecular targets. This study aimed to evaluate the potential of natural compounds and chemicals against RNA viruses using a three-tiered approach to molecular docking. Binding scores obtained from ChemPLP revealed that natural compounds and repurposed drugs exhibited strong affinities for the binding sites on angiotensin-converting enzyme 2 (ACE2) receptors in host cells, the receptorbinding domain (RBD) site of the RBD-ACE2 complex, PL pro , and 3CL pro . Conclusively, these findings suggest that alternative medicines and antiviral drug repurposing strategies may provide promising therapeutic remedies for patients with COVID-19, along with further validation via preclinical and clinical trials.
Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the respiratory illness that led to the coronavirus disease 2019 (COVID-19) pandemic, which began in late 2019 ( Acter et al., 2020) . The COVID-19 pandemic originated in December 2019 at the Seafood Market in Wuhan, China. The virus rapidly spread to Thailand, Japan, South Korea, Singapore, and Iran.
Declaration of Competing Interest The authors declare no conflict of interest.
Consent for publication All Authors listed have seen and approved the manuscript being submitted.
Appendix A. Supporting information Supplementary data associated with this article can be found in the online version at doi:10.1016/j.phytol.2025.102999.
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