In silico Screening of Potential Drug Candidate against Chain a of Coronavirus Binding Protein from Major Nigella Bioactive Compounds

Abstract

Background: More hazardous varieties of severe acute respiratory syndrome-related coronavirus have created major health hazards around the globe since 2019. There is no hundred percent effective drug has been developed against this virus. Bioactive compounds from plants are used as drugs or the main source of raw material for drugs against various diseases. Aims: To screen the potential drug candidate against coronavirus from major Nigella bioactive compounds. Methods and Materials: In the first step of our computational biology-dependent study, we selected six major Nigella compounds, four major drugs used in COVID-19 treatment, and a binding protein of coronavirus. In the second step, we processed the ligands and peptides and performed a docking to test the binding affinity. In the final step, we selected a compound with the highest binding affinity and performed molecular simulation, ADME/T, bioactivity, and QSAR analysis to characterize this molecule as a drug candidate. Results: Four different antiviral agents that had been used in the treatment of COVID-19 patients showed less binding affinity in molecular docking compared with six bioactive compounds of Nigella. Nigellamine C, Nigeglanine, nigellamine D, nigellicine, nigellidine, and nigellone showed binding affinity of -7.9, -7.5, -7.3, -6.5, -7, and -6.7 kcal/mol, respectively whereas ribavirin, favipiravir, remdesivir, and nirmatrelvir showed -5.1, -4.8, -6.2, and -5.9 kcal/mol, accordingly to chain A of subunit 1 (S1) of the spike protein of coronavirus. Nigellamine C showed the highest binding affinity and suitable ADME/T properties with negligible toxic properties and good drug-likeness properties. Conclusion: Nigellamine C may be a potent candidate for inhalation and/or oral drug development based on QSAR analysis and ADME/T analysis among all Nigella compounds.