Utilizing natural compounds as ligands to disrupt the binding of SARS-CoV-2 receptor-binding domain to angiotensin-converting enzyme 2, impeding viral infection

Currently, no specific antiviral drug has been definitively proven effective in treating patients with severe coronavirus disease 2019 (COVID-19). 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 receptor-binding 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. • The natural products curcumin and arachidonic acid had distinct binding to the ACE2 (Angiotensin-Converting Enzyme 2), RBD (Receptor-Binding Domain) and the RBD-ACE2 complex binding site. • Strong interactions were observed with Papain-like protease and 3C-like protease of COVID-19. • These repurposed drugs also strongly interacted with Papain-like protease and 3C-like protease of SARS-CoV-2. • Docking calculations supported these compounds as a potential remedy for the COVID-19 pandemic.