Virtual screening of phytoconstituents from miracle herb targeting nucleocapsid protein and papain-like protease of SARS-CoV-2 for COVID-19 treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coronavirus disease 2019 (COVID-19). , commonly known as black seed or black cumin, has been a historical and traditional plant since thousands of years. Based on their therapeutic efficacy, the chief components of terpenoids and flavonoids were selected from seeds and seed oil. This study was designed to check the antiviral efficacy of main phytoconstituents against five potential targets of SARS-CoV-2 using structure-based virtual screening approach. Out of twenty five phytocomponents, ten components showed best binding affinity against two viral proteins N-terminal RNA binding domain (NRBD; PDB ID: 6M3M) of nucleocapsid protein and papain-like protease (PL-; PDB ID: 6W9C) of SARS-CoV-2 using AutoDock 4.2.6, AutoDock Vina and iGEMDOCK. PASS analyses of all ten phytocomponents using Lipinski's Rule of five showed promising results. Further, druglikeness and toxicity assessment using OSIRIS Data Warrior v5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. Molecular dynamics simulation study of NRBD of SARS-CoV-2 nucleocapsid protein-alpha-spinasterol complex and PL--cycloeucalenol complex displayed strong stability at 300 K. Both these complexes exhibited constant root mean square deviation (RMSDs) of protein side chains and Cα atoms throughout the simulation run time. Interestingly, PL- and NRBD are key proteins in viral replication, host cell immune evasion and viral assembly. Thus, NRBD and PL- have the potential to serve as therapeutic targets for phytoconstituents in drug discovery process against COVID-19.