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

Sahabjada Siddiqui; Shivbrat Upadhyay; Rumana Ahmad; Anamika Gupta; Aditi Srivastava; Anchal Trivedi; Ishrat Husain; Bilal Ahmad; Maqusood Ahamed; Mohsin Ali Khan

doi:10.1080/07391102.2020.1852117

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

J Biomol Struct Dyn. 2022 Jun;40(9):3928-3948. doi: 10.1080/07391102.2020.1852117. Epub 2020 Dec 8.

Authors

Affiliations

¹ Deparment of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India.
² Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India.
³ Research Cell, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India.
⁴ King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.
⁵ Chancellor, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coronavirus disease 2019 (COVID-19). Nigella sativa, 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 N. sativa seeds and seed oil. This study was designed to check the antiviral efficacy of N. sativa main phytoconstituents against five potential targets of SARS-CoV-2 using in silico structure-based virtual screening approach. Out of twenty five phytocomponents, ten components showed best binding affinity against two viral proteins viz. N-terminal RNA binding domain (NRBD; PDB ID: 6M3M) of nucleocapsid protein and papain-like protease (PL-_PRO; 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-_PRO-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-_PRO and NRBD are key proteins in viral replication, host cell immune evasion and viral assembly. Thus, NRBD and PL-_PRO have the potential to serve as therapeutic targets for N. sativa phytoconstituents in drug discovery process against COVID-19.

Keywords: Nigella sativa; SARS-CoV-2; molecular chemoinformatics; nucleocapsid protein; papain-like protease; phytocomponents.

MeSH terms

Antiviral Agents* / chemistry
COVID-19 Drug Treatment
Coronavirus Nucleocapsid Proteins* / antagonists & inhibitors
Coronavirus Papain-Like Proteases* / antagonists & inhibitors
Humans
Molecular Docking Simulation
Molecular Dynamics Simulation
Nigella sativa* / chemistry
Phosphoproteins / antagonists & inhibitors
Protease Inhibitors / chemistry
SARS-CoV-2* / drug effects

Substances

Antiviral Agents
Coronavirus Nucleocapsid Proteins
Phosphoproteins
Protease Inhibitors
nucleocapsid phosphoprotein, SARS-CoV-2
Coronavirus Papain-Like Proteases
papain-like protease, SARS-CoV-2

Grants and funding

The authors gratefully acknowledge Dr. Meraj Ahmad, Professor, Dept. of Sociology, University of Lucknow, Lucknow, India, for being the inspiration and motivation behind the present work in view of his exceptional work and contribution in the area of social sciences, humanities and public health. Maqusood Ahamed is also grateful to the Researchers Supporting Project number (RSP- 2020/129), King Saud University, Riyadh, Saudi Arabia.