In silico identification of compounds from Nigella sativa seed oil as potential inhibitors of SARS-CoV-2 targets

Bulletin of the National Research Centre - Tập 45 Số 1 - 2021
Chidi Edbert Duru1, Ijeoma Akunna Duru2, Abayomi Emmanuel Adegboyega3
1Surface Chemistry and Environmental Technology (SCENT) Research Unit, Department of Chemistry, Imo State University, Owerri, Imo State, Nigeria
2Department of Chemistry, Federal University of Technology, Owerri, Imo State, Nigeria
3Department of Biochemistry, Faculty of Medical Sciences, University of Jos, Jos, Plateau State, Nigeria

Tóm tắt

Abstract 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–angiotensin-converting 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.

Từ khóa


Tài liệu tham khảo

Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ (2010) Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic β-cells of streptozotocin-induced diabetic rats. J Diabetes 2(4):256–266

Adeoye-Isijola MO, Olajuyigbe OO, Jonathan SG, Coopoosamy RM (2018) Bioactive compounds in ethanol extract of Lentinus squarrosulus mont - a Nigerian medicinal macrofungus. Afr J Tradit Complement Altern Med 15(2):42–50

Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA et al (2013) A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed 3(5):337–352

Al YM (1986) Phytochemical studies of the plants used in traditional medicine of Saudi Arabia. Fitoterapia 57:179–182

Awadalla EA (2012) Ameliorative effect of the crude oil of the Nigella sativa on oxidative stress induced in rat testes by cisplatin treatment. Biomed Prev Nutr 2:265–268

Balamurugan M, Selvam GG, Thinakaran T, Sivakumar K. Biochemical study and GC-MS analysis of Hypnea musciformis (Wulf.) Lamouroux Am-Euras. J Sci Res. 2013; 8(3):117–123.

Begum IF, Mohankumar R, Jeevan M, Ramani K (2016) GC-MS analysis of bioactive molecules derived from Paracoccus pantotrophus FMR19 and the antimicrobial activity against bacterial pathogens and MDROs. Indian J Microbiol 56:426–432

BIOVIA, Dassault Systemes, San Diego, Discovery studio modeling environment, 2020.

Caboni P, Ntalli NG, Aissani N, Cavoski I, Angioni A (2012) Nematicidal activity of (E, E)-2,4-decadienal and (E)-2-decenal from Ailanthus altissima against Meloidogyne javanica. J Agric Food Chem 60(4):1146–1151

Chavan M, Wakte P, Shinde D (2010) Analgesic and anti-inflammatory activity of cryophyllene oxide from Annona squamosa leaf bark. Phytomedicine 17(2):149–151

Datta AK, Saha A, Bhattacharya A, Mandal A, Paul R Sonali SS. Black cumin (Nigella sativa L.) - A review. J Plant Dev Sci. 2012; 4(1):1–43.

Duru CE (2020) Mineral and phytochemical evaluation of Zea mays husk. Sci Afr 7:e00224. https://doi.org/10.1016/j.sciaf.2019.e00224

Duru CE, Duru IA, Bilar A (2020) Computational investigation of sugar fermentation inhibition by bergenin at the pyruvate decarboxylate isoenzyme 1 target of Scharomyces cervisiae. J Med Plants Stud 8(6):21–25

Duru IA, Duru CE (2020) Molecular docking of compounds in the essential oil of Ocimium gratissimum leaf against PIM-1 kinase of Escherichia coli. Ej-Chem 1(6):1–4

El-Sawi SA, Maamoun AA, Salama AH, Farghaly AA (2020) Chemical profiling of Thevetia peruviana leaves cytotoxic active extracts enhanced by microemulsion formulation. Bull Natl Res Cent 44:93. https://doi.org/10.1186/s42269-020-00339-3

Engel G, Brinkmann J (2017) Nigella- Nigella sativa, Ranunculaceae. HerbalGram 114:8–16

Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L et al (2020) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 368(6492):779–782

Guy JL, Jackson RM, Jensen HA, Hooper NM, Turner AJ (2005) Identification of critical active-site residues in angiotensin-converting enzyme-2 (ACE2) by site-directed mutagenesis. FEBS J 272(14):3512–3520

Hadi MY, Mohammed GJ, Hameed IH (2016) Analysis of bioactive chemical compounds of Nigella sativa using gas chromatography-mass spectrometry. J Pharmacognosy Phytother 8(2):8–24

http://sts.bioe.uic.edu/castp/index.html?j_5f45dd381f58d

Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y et al (2020) Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 582(7811):289–293

Johnson TO, Odoh KD, Akinanmi AO, Adegboyega AE (2020) Biochemical evaluation and molecular docking assessment of the anti-inflammatory potential of Phyllanthus nivosus leaf against ulcerative colitis. Heliyon 6:e03893. https://doi.org/10.1016/j.heliyon.2020.e03893

Kamil ZH (2013) Spectacular black seeds (Nigella sativa): Medical importance review. Med J Babylon 10(4):1–9

Konkolova E, Klima M, Nencka R, Boura E (2020) Structural analysis of the putative SARS-CoV-2 primase complex. J Struct Biol 211(2):107548. https://doi.org/10.1016/j.jsb.2020.107548

Kumar Y, Singh H, Patel CN (2020). 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. 2020; 13(9):1210–1223.

Lang G, Buchbauer G (2012) A review on recent research results (2008–2010) on essential oils as antimicrobials and antifungals. A review Flavour Fragr J 27(1):13–39

Lipinski CA (2016) Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions. Adv Drug Deliv Rev 101:34–41

Marques FM, Figueira MM, Schmitt EFP, Kondratyuk TP, Endringer DC, Scherer R et al (2019) In vitro anti-inflammatory activity of terpenes via suppression of superoxide and nitric oxide generation and the NF-κB signalling pathway. Inflammopharmacology 27(2):281–289

Michalska K, Kim Y, Jedrzejczak R, Maltseva NI, Stols L, Endres M, Joachimiak A (2020) Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes. IUCrJ 7(Pt 5):814–824

Muniyan R, Gurunathan J (2016) 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 54(12):2814–2821

Naz H (2011) Nigella sativa: the miraculous herb. Pak J Biochem Mol Biol 44:44–48

Peng L, Liu A, Shen Y, Xu H, Yang S, Ying X et al (2013) Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-κB pathway. Oncol Rep 29(2):571–578

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera- a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612

Punch Newspaper, April 7, 2020. https://healthwise.punchng.com/i-fought-covid-19-with-vitamin-c-black-seed-oil-mixed-with-honey-gov-makinde-2/

Saeed NM, El-Demerdash E, Abdel-Rahman HM, Algandaby MM, Al-Abbasi FA, Abdel-Naim AB. Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models. Toxicol Appl Pharmacol. 2012; 1:264(1):84–93.

Shariq IM, Israil AM, Iqbal A, Brijesh P. Morpho-physiological characterization of seeds and seedlings of Nigella sativa Linn.: Study on Indian germplasm. Int Res J Biol Sci. 2015; 4(4):38–42.

Sharma N, Ahirwar D, Jhade D, Gupta S (2009) Medicinal and phamacological potential of Nigella sativa: A review. Ethnobot Rev 13:946–955

Sultan MT, Butt MS, Karim R, Iqbal SZ, Ahmad S, Zia-UI-Haq M et al (2014) Effect of Nigella sativa fixed and essential oils on antioxidant status, hepatic enzymes, and immunity in streptozotocin induced diabetes mellitus. BMC Complement Altern Med 14:193. https://doi.org/10.1186/1472-6882-14-193

Tan K, Kim Y, Jedrzejczak R, Maltseva N, Endres M, Michalska K, Joachimiak A. The crystal structure of Nsp9 RNA binding protein of SARS CoV-2. Center for Structural Genomics of Infectious Diseases (CSGID); 2020. https://doi.org/https://doi.org/10.2210/pdb6W4B/pdb

Tian W, Chen C, Lei X, Zhao J, Liang J. CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res. 2018; 46:363–367.

Tsao YC, Chang YJ, Wang CH, Chen L (2020) Discovery of isoplumbagin as a novel NQO1 substrate and anti-cancer quinone. Int J Mol Sci 21(12):4378. https://doi.org/10.3390/ijms21124378

Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA (2012) Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Interact 197(1):40–46

Vavilov NI, Dorofeev VF (1992) Origin and Geography of Cultivated Plants. Cambridge University Press, Cambridge, UK

Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z et al (2020) Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 181(4):894–904

WHO. Novel coronavirus (2019-nCoV), 2020. https://www.euro.who.int/en/health-topics/health-emergencies/novel-coronavirus-2019-ncov_old.

Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J et al (2020) Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature 585(7824):273–276

Wu JHY, Marklund M, Imamura F, Tintle N, Ardisson Korat AV, de Goede J et al (2017) 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 5(12):965–974

Yang H, Lou C, Sun L, Li J, Cai Y, Wang Z, et al. admetSAR 2.0: Wed-service for prediction and optimization of chemical ADMET properties. Bioinformatics (Oxford, England), 2019; 35(6):1067–1069.

Yimer EM, Tuem KB, Karim A, Ur-Rehman N, Anwar F. Nigella sativa L. (Black Cumin): A promising natural remedy for wide range of illnesses. Evid Based Complement Alternat Med. 2019; 1528635. https://doi.org/10.1155/2019/1528635

Zhao Z, Vavrusova M, Skibsted LH (2018) Antioxidant activity and calcium binding of isomeric hydroxybenzoates. J Food Drug Anal 26(2):591–598

Zhong HA (2017) ADMET properties: overview and current topics. In: Grover A (ed) Drug design: principles and applications. Springer, Singapore, pp 113–133

Thông tin
Thông tin xuất bản

Bulletin of the National Research Centre

Tập 45 Số 1

Thông tin tác giả