Virtual screening, ADMET profiling, PASS prediction, and bioactivity studies of potential inhibitory roles of alkaloids, phytosterols, and flavonoids against COVID-19 main protease (M(pro))

Abdul-Hammed, Misbaudeen; Adedotun, Ibrahim Olaide; Olajide, Monsurat; Irabor, Christianah Otoame; Afolabi, Tolulope Irapada; Gbadebo, Ibrahim Olajide; Rhyman, Lydia; Ramasami, Ponnadurai

The current research used a virtual screening method to study 57 isolated phytochemicals (alkaloids, phytosterols, and flavonoids) against the SARS-CoV-2 main protease (M(pro)). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the selected compounds were analysed using admetSAR tool while SwissADME and Molinspiration chemoinformatics tools were used to examine the oral bioavailability and drug-likeness properties. Parameters such as physicochemical properties, activity spectra for substances (PASS) prediction, bioactivity, binding mode, and molecular interactions were also analysed. Our results favoured Lupeol (–8.6 kcal/mol), Lupenone (–7.7 kcal/mol), Hesperetin (–7.4 kcal/mol), Apigenin (–7.3 kcal/mol) and Castasterone (–7.3 kcal/mol) as probable inhibitors of SARS-CoV-2. This is because of their good binding affinities, bioactivities, drug-likeness, ADMET properties, PASS properties, oral bioavailability, binding mode and their interactions with the active site of the target receptor compared to Remdesivir and Azithromycin. Therefore, these compounds could be explored towards the development of new therapeutic agents against SARS-CoV-2.