Molecular Docking and Admet Analyses of Photochemicals from Nigella sativa (blackseed), Trigonella foenum-graecum (Fenugreek) and Anona muricata (Soursop) on SARS-CoV-2 Target

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) responsible for the 2019 coronavirus disease (COVID-19) has caused a global health challenge. The SARS-COV-2 main protease, 3CLpro/Mpro plays a critical role in the viral gene expression and replication and has been a major target for inhibiting viral maturation and enhancing host innate immune responses against COVID-19. In this study, we screened a library of 38 phytochemicals from Nigella sativa (blackseed), Trigonella foenum-graecum (Fenugreek) and Anona muricata (Soursop) potent medicinal plants with reported antiviral properties - in a molecular docking protocol on 3CLpro using Autodock4.0 tool implanted in PyRx followed by docking validation and insilico absorption, distribution, metabolism, excretion, and toxicology (ADMET) evaluations. The docking results were visualized using Accelrys Discovery Studio and Pymol software. Among the 38 ligands screened, 19 showed significant interaction through non-covalent hydrogen bonding, hydrophobic, and electrostatic interactions with binding affinities from -5.3kcal/mol to -8.1kcal/mol indicating significant binding interactions at the active site binding pocket. Another important interaction observed in the study which mostly involve the transfer of charges was pi-interactions such as Pi-Pi interaction, Pi-Alkyl interaction, Pi-Sulfur interaction, Pi- Sigma, and Pi-Pi stacking. The docking results revealed that phytochemicals from T. foenum-graecum showed more 3CLpro inhibitory potential compared to those from N. sativa and A. muricata. Insilico ADMET evaluations for drug-like and lead-like characteristics however demonstrated that only 8 ligands - apigenin, kaempferol, luteolin, dithymoquinone, naringenine, nornuciferine, quercetin and nigellidine were actually drug-like; showed best activities against 3CLpro, and lack hepatotoxicity effects while none was lead-like. Insilico results of this study further suggested that drug repurposing candidates, remdesivir, indinavir,hydroxychloroquine, chloroquine and ritonavir,exhibited various interactions with 3CLpro. Hence, further in vitro and in vivo studies are proposed.