In silico identification of compounds from Nigella sativa seed oil as potential inhibitors of SARS-CoV-2 targets
Chidi Edbert Duru, Ijeoma Akunna Duru, Abayomi Emmanuel Adegboyega
Bulletin of the National Research Centre, doi:10.1186/s42269-021-00517-x
Background: The growing number of cases, severity and fatality of the COVID-19 pandemic, coupled with the fact that no cure has been found has made infected individuals especially in Africa, to resort to the consumption of different natural products to alleviate their condition. One of such plant materials that have been consumed to remedy the severity of this viral infection is the oil of Nigella sativa seed commonly called black seed oil. In this study, we extracted and characterized the oil from this seed using gas chromatography coupled to a mass selective detector to identify the component phytochemicals. Site-directed multiligand docking of the identified compounds was performed on SARS-CoV-2 molecular targets-Replicase polyprotein 1a, RNA binding protein of NSP9, ADP ribose phosphatase of NSP3, 3-chymotrypsin-like protease 3CLpro, and RNA-dependent RNA polymerase RDRP, and ACE2-angiotensinconverting enzyme from the Homo sapiens.
Results: The binding affinity of caryophyllene oxide was the highest on 3CLpro (− 6.0 kcal/mol), NSP3 (− 6.3 kcal/ mol), NSP9 (− 6.3 kcal/mol), and RDRP (− 6.9 kcal/mol) targets, while α-bergamotene gave the best binding affinity on RPIA (5.7 kcal/mol) target. The binding affinity of β-bisabolene on the ACE2 target (− 8.0 kcal/mol) was almost the same as Remdesivir (− 8.1 kcal/mol). The ADMET properties of these three phytochemicals showed that they are good drug leads for these SARS-CoV-2 receptors.
Conclusion: The findings from this study strongly indicate that the reported recovery from COVID-19 infection claimed by patients who consumed black seed oil could be linked to the presence of caryophyllene oxide, α-bergamotene, and β-bisabolene in this natural product.
Abbreviations COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; GC-MS: Gas chromatography-mass spectrometer; MSD: Mass selective detector; NIST: National Institute of Standards and Technology; RP1A: Replicase polyprotein; NSP9: Nonstructural protein 9; NSP3: Nonstructural protein 3; 3CLpro: 3-Chymotrypsin-like protease; RDRP: RNAdependent RNA polymerase; ACE2: Angiotensin-converting enzyme; CASTp: Computed atlas for surface topography of proteins; ADMET: Absorption, distribution, metabolism and elimination and toxicity; FDA: Food and drug administration; TYR : Tyrosine; MET: Methionine; TRP: Tryptophan; ILE: Isoleusine; SER: Serine; ALA: Alanine; PHE: Phenylalanine; THR: Threonine; VAL: Valine; ARG : Arginine; PRO: Proline; LEU: Leucine; HIS: Histidine; ASN: Asparagine; GLY: Glycine; LYS: Lysine; GLU: Glutathione.
Authors' contributions CED conceived, designed, and wrote the research, and performed the DFT studies. IAD extracted and characterized the oil sample, and proof-read the manuscript. AEA performed the docking studies and post docking analysis. All authors have approved the manuscript in the present form and gave the permission to submit the manuscript for publication. All authors read and approved the final manuscript.
Funding No funds, grants, or other support was received.
Ethics approval and consent to participate Not applicable.
Consent for publication Not applicable.
Competing interests The authors declare..
Ahmad, Husain, Mujeeb, Khan, Najmi et al., A review on therapeutic potential of Nigella sativa: A miracle herb, Asian Pac J Trop Biomed
Al, Phytochemical studies of the plants used in traditional medicine of Saudi Arabia, Fitoterapia
Awadalla, Ameliorative effect of the crude oil of the Nigella sativa on oxidative stress induced in rat testes by cisplatin treatment, Biomed Prev Nutr
Balamurugan, Selvam, Thinakaran, Sivakumar, Biochemical study and GC-MS analysis of Hypnea musciformis (Wulf.) Lamouroux Am-Euras, J Sci Res
Begum, Mohankumar, Jeevan, Ramani, GC-MS analysis of bioactive molecules derived from Paracoccus pantotrophus FMR19 and the antimicrobial activity against bacterial pathogens and MDROs, Indian J Microbiol
Biovia, Systemes, Discovery studio modeling environment
Caboni, Ntalli, Aissani, Cavoski, Angioni, Nematicidal activity of (E, E)-2,4-decadienal and (E)-2-decenal from Ailanthus altissima against Meloidogyne javanica, J Agric Food Chem
Chavan, Wakte, Shinde, Analgesic and anti-inflammatory activity of cryophyllene oxide from Annona squamosa leaf bark, Phytomedicine
Datta, Saha, Bhattacharya, Mandal, Sonali, Black cumin (Nigella sativa L.) -A review, J Plant Dev Sci
Duru, Duru, Bilar, Computational investigation of sugar fermentation inhibition by bergenin at the pyruvate decarboxylate isoenzyme 1 target of Scharomyces cervisiae, J Med Plants Stud
Duru, Duru, Molecular docking of compounds in the essential oil of Ocimium gratissimum leaf against PIM-1 kinase of Escherichia coli, Ej-Chem
El-Sawi, Maamoun, Salama, Farghaly, Chemical profiling of Thevetia peruviana leaves cytotoxic active extracts enhanced by microemulsion formulation, Bull Natl Res Cent, doi:10.1186/s42269-020-00339-3
Engel, Brinkmann, Nigella-Nigella sativa, Ranunculaceae, Herbal-Gram
Fakhoury, Kamal, Wafai, Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic β-cells of streptozotocin-induced diabetic rats
Gao, Yan, Huang, Liu, Zhao et al., Structure of the RNA-dependent RNA polymerase from COVID-19 virus, Science
Guy, Jackson, Jensen, Hooper, Turner, Identification of critical active-site residues in angiotensin-converting enzyme-2 (ACE2) by site-directed mutagenesis, FEBS J
Hadi, Mohammed, Hameed, Jin, Xu et al., Analysis of bioactive chemical compounds of Nigella sativa using gas chromatography-mass spectrometry, J Pharmacognosy Phytother
Johnson, Odoh, Akinanmi, Adegboyega, Biochemical evaluation and molecular docking assessment of the anti-inflammatory potential of Phyllanthus nivosus leaf against ulcerative colitis, Heliyon, doi:10.1016/j.heliyon.2020.e03893
Kamil, Spectacular black seeds (Nigella sativa): Medical importance review, Med J Babylon
Kumar, Singh, Patel, In silico prediction of potential inhibitors for the Main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing, J Infect Public Health
Lang, Buchbauer, A review on recent research results (2008-2010) on essential oils as antimicrobials and antifungals, A review Flavour Fragr J
Lipinski, Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions, Adv Drug Deliv Rev
Marques, Figueira, Schmitt, Kondratyuk, Endringer et al., In vitro anti-inflammatory activity of terpenes via suppression of superoxide and nitric oxide generation and the NF-κB signalling pathway, Inflammopharmacology
Michalska, Kim, Jedrzejczak, Maltseva, Stols et al., Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes, IUCrJ
Mo, Olajuyigbe, Jonathan, Coopoosamy, Bioactive compounds in ethanol extract of Lentinus squarrosulus mont -a Nigerian medicinal macrofungus, Afr J Tradit Complement Altern Med
Muniyan, Gurunathan, Lauric acid and myristic acid from Allium sativum inhibit the growth of Mycobacterium tuberculosis H37Ra: in silico analysis reveals possible binding to protein kinase B, Pharm Biol
Naz, Nigella sativa: the miraculous herb, Pak J Biochem Mol Biol
Peng, Liu, Shen, Xu, Yang et al., Antitumor and antiangiogenesis effects of thymoquinone on osteosarcoma through the NF-κB pathway, Oncol Rep
Pettersen, Goddard, Huang, Couch, Greenblatt et al., UCSF Chimera-a visualization system for exploratory research and analysis, J Comput Chem
Saeed, El-Demerdash, Abdel-Rahman, Algandaby, Al-Abbasi et al., Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models, Toxicol Appl Pharmacol
Shariq, Israil, Iqbal, Brijesh, Morpho-physiological characterization of seeds and seedlings of Nigella sativa Linn.: Study on Indian germplasm, Int Res J Biol Sci
Sharma, Ahirwar, Jhade, Gupta, Medicinal and phamacological potential of Nigella sativa: A review, Ethnobot Rev
Sultan, Butt, Karim, Iqbal, Ahmad et al., Effect of Nigella sativa fixed and essential oils on antioxidant status, hepatic enzymes, and immunity in streptozotocin induced diabetes mellitus, BMC Complement Altern Med, doi:10.1186/1472-6882-14-193
Tan, Kim, Jedrzejczak, Maltseva, Endres et al., The crystal structure of Nsp9 RNA binding protein of SARS CoV-2, doi:10.2210/pdb6W4B/pdb
Tian, Chen, Lei, Zhao, Liang, CASTp 3.0: computed atlas of surface topography of proteins, Nucleic Acids Res
Tsao, Chang, Wang, Chen, Discovery of isoplumbagin as a novel NQO1 substrate and anti-cancer quinone, Int J Mol Sci, doi:10.3390/ijms21124378
Umar, Zargan, Umar, Ahmad, Katiyar et al., Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats, Chem Biol Interact
Vavilov, Dorofeev, Origin and Geography of Cultivated Plants
Wang, Zhang, Wu, Niu, Song et al., Structural and functional basis of SARS-CoV-2 entry by using human ACE2, Cell
Who, Novel coronavirus (2019-nCoV)
Williamson, Feldmann, Schwarz, Meade-White, Porter et al., Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2, Nature
Wu, Marklund, Imamura, Tintle, Korat et al., Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies, Lancet Diabetes Endocrinol
Yang, Lou, Sun, Li, Cai et al., admetSAR 2.0: Wed-service for prediction and optimization of chemical ADMET properties, Bioinformatics
Yimer, Tuem, Karim, Ur-Rehman, Anwar, Nigella sativa L. (Black Cumin): A promising natural remedy for wide range of illnesses, Evid Based Complement Alternat Med, doi:10.1155/2019/1528635
Zhao, Vavrusova, Skibsted, Antioxidant activity and calcium binding of isomeric hydroxybenzoates, J Food Drug Anal
Zhong, ADMET properties: overview and current topics