Dual SARS-CoV-2 and MERS-CoV inhibitors from : isolation, structure elucidation, molecular modelling studies, and activities.

The COVID-19 pandemic has spread throughout the whole globe, so it is imperative that all available resources be used to treat this scourge. In reality, the development of new pharmaceuticals has mostly benefited from natural products. The widespread medicinal usage of species in the Asteraceae family is extensively researched. In this study, compounds isolated from methanolic extract of Delile, a wild plant whose grows in Egypt's Sinai Peninsula. Three compounds, stigmasterol 3--β-D-glucopyranoside 1, rhamnetin 3, and padmatin 6, were first isolated from this species. In addition, five previously reported compounds, arcapillin 2, jaceosidin 4, hispidulin 5, 7--methyleriodictyol 7, and eupatilin 8, were isolated. Applying molecular modelling simulations revealed two compounds, arcapillin 2 and rhamnetin 3 with the best docking interactions and energies within SARS-CoV-2 M-binding site (-6.16, and -6.70 kcal mol, respectively). The top-docked compounds (2-3) were further evaluated for inhibitory concentrations (IC), and half-maximal cytotoxicity (CC) of both SARS-CoV-2 and MERS-CoV. Interestingly, arcapillin showed high antiviral activity towards SARS-CoV-2 and MERS-CoV, with IC values of 190.8 μg mL and 16.58 μg mL, respectively. These findings may hold promise for further preclinical and clinical research, particularly on arcapillin itself or in collaboration with other drugs for COVID-19 treatment.