Generic placeholder image

Coronaviruses

Author(s): S.L. Khan*, F.A. Siddiqui, S.P. Jain and G.M. Sonwane

DOI: 10.2174/2666796701999200921094103

DownloadDownload PDF Flyer Cite As
Discovery of Potential Inhibitors of SARS-CoV-2 (COVID-19) Main Protease (Mpro) from Nigella Sativa (Black Seed) by Molecular Docking Study

Page: [384 - 402] Pages: 19

  • * (Excluding Mailing and Handling)

Abstract

Purpose: A new human coronavirus (SARS-CoV-2), triggering pneumonia, is termed as Coronavirus Disease-19 (COVID-19). There is an alarming situation now as this new virus is spreading around the world. At present, there are no specific treatments for COVID-19. Nigella sativa is known as Prophetic Medicine as its use has been mentioned in Prophetic Hadith, as a natural remedy for all the diseases except death. Seeds and oils of N. sativa have a long history of folklore usage in various systems of medicine such as Unani and Tibb, Ayurveda and Siddha in the treatment of different diseases and ailments. The aim of this research is to provide a potential inhibitor of SARS-CoV-2 Mpro.

Methods: The Molecular docking tool was used to optimize the binding affinities of chemical constituents of N. sativa with SARS-CoV-2 Mpro.

Results: Many constituents from N. Sativa have shown better binding affinity than reported drugs with SARS-CoV-2 Mpro i.e., the alpha-hederin, Stigmasterol glucoside, Nigellidine-4-O-sulfite, Nigellidine, Sterol-3-β-D-glucoside, Dithymoquinone, beta-sitosterol have binding affinities (kcal/mol) of -9, -8.1, -8, -7.7, -7.7, -7.4, -7.4, and -6.9 and number of hydrogen bonds formed are 06, 04, 03, 03, 03, 00, and 01, respectively.

Conclusion: There is rationale and pre-clinical evidence of the effectiveness of N. Sativa that it may be helpful for the treatment of COVID-19 and can serve as a potential natural candidate. However, more studies should be conducted to collect high-quality data and scientific evidence of N. Sativa to use it against COVID-19 clinically.

Keywords: SARS-CoV-2 Mpro, Nigella sativa (black seed), molecular docking, PyRx virtual screening tool, COVID-19, coronavirus.

Graphical Abstract

[1]
Wang L, Wang Y, Ye D, Liu Q. Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence. Int J Antimicrob Agents 2020; 55(6)105948
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105948.]
[2]
Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking study. Life Sci 2020; 253117592
[http://dx.doi.org/10.1016/j.lfs.2020.117592]]
[3]
Singh AK, Singh A, Shaikh A, Singh R, Misra A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: a systematic search and a narrative review with a special reference to India and other developing countries. Diabetes Metab Syndr Clin Res Rev 2020; 14(3): 241-6.
[http://dx.doi.org/10.1016/j.dsx.2020.03.011.]]
[4]
Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020; 109102433
[http://dx.doi.org/10.1016/j.jaut.2020.102433.]]
[5]
Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020; 57: 279-83.
[http://dx.doi.org/10.1016/j.jcrc.2020.03.005.]] [PMID: 32173110]
[6]
Ahmad A, Husain A, Mujeeb M, et al. A review on therapeutic potential of Nigella sativa: a miracle herb. Asian Pac J Trop Biomed 2013; 3(5): 337-52.
[http://dx.doi.org/10.1016/S2221-1691(13)60075-1] [PMID: 23646296]
[7]
Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar M. Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie 2000; 55(3): 379-82.
[PMID: 10967716]
[8]
Dehkordi FR, Kamkhah AF. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundam Clin Pharmacol 2008; 22(4): 447-52.
[http://dx.doi.org/10.1111/j.1472-8206.2008.00607.x] [PMID: 18705755]
[9]
Haseena S, Aithal M, Das KK, Saheb SH. Phytochemical analysis of Nigella sativa and its effect on reproductive system. J Pharm Sci Res 2015; 7(8): 514-7.
[10]
Khan MA, Chen HC, Tania M, Zhang DZ. Anticancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med 2011; 8(5)(Suppl.): 226-32.
[http://dx.doi.org/10.4314/ajtcam.v8i5S.10] [PMID: 22754079]
[11]
Randhawa MA, Alghamdi MS. Anticancer activity of Nigella sativa (black seed) - a review. Am J Chin Med 2011; 39(6): 1075-91.
[http://dx.doi.org/10.1142/S0192415X1100941X] [PMID: 22083982]
[12]
Majdalawieh AF, Fayyad MW. Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: a comprehensive review. Int Immunopharmacol 2015; 28(1): 295-304.
[http://dx.doi.org/10.1016/j.intimp.2015.06.023] [PMID: 26117430]
[13]
Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol 2005; 5(13-14): 1749-70.
[http://dx.doi.org/10.1016/j.intimp.2005.06.008] [PMID: 16275613]
[14]
Amin B, Hosseinzadeh H. Black cumin (Nigella sativa) and its active constituent, thymoquinone: an overview on the analgesic and anti-inflammatory effects. Planta Med 2016; 82(1-2): 8-16.
[PMID: 26366755]
[15]
Hanafy MSM, Hatem ME. Studies on the antimicrobial activity of Nigella sativa seed (black cumin). J Ethnopharmacol 1991; 34(2-3): 275-8.
[http://dx.doi.org/10.1016/0378-8741(91)90047-H] [PMID: 1795532]
[16]
Alenzi FQ. Antioxidant properties of Nigella sativa. J Mol Genet Med 2013; 7(3): 1-5.
[http://dx.doi.org/10.4172/1747-0862.1000077]
[17]
Gholamnezhad Z, Havakhah S, Boskabady MH. Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: a review. J Ethnopharmacol 2016; 190: 372-86.
[http://dx.doi.org/10.1016/j.jep.2016.06.061] [PMID: 27364039]
[18]
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. Evidence-based complement. Altern Med 2019; 20191528635
[http://dx.doi.org/10.1155/2019/1528635]
[19]
Forouzanfar F, Bazzaz BS, Hosseinzadeh H. Black cumin (Nigella sativa) and its constituent (thymoquinone): a review on antimicrobial effects. Iran J Basic Med Sci 2014; 17(12): 929-38.
[PMID: 25859296]
[20]
Al-Jassir MS. Chemical composition and microflora of black cumin (Nigella sativa L.) seeds growing in Saudi Arabia. Food Chem 1992; 45(4): 239-42.
[http://dx.doi.org/10.1016/0308-8146(92)90153-S]
[21]
Cheikh-Rouhou S, Besbes S, Hentati B, Blecker C, Deroanne C, Attia H. Nigella sativa L.: chemical composition and physicochemical characteristics of lipid fraction. Food Chem 2007; 101(2): 673-81.
[http://dx.doi.org/10.1016/j.foodchem.2006.02.022]
[22]
Ali Z, Ferreira D, Carvalho P, Avery MA, Khan IA. Nigellidine-4-O-sulfite, the first sulfated indazole-type alkaloid from the seeds of Nigella sativa. J Nat Prod 2008; 71(6): 1111-2.
[http://dx.doi.org/10.1021/np800172x] [PMID: 18471018]
[23]
Nickavar B, Mojab F, Javidnia K, Amoli MA. Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran. Z Natforsch C J Biosci 2003; 58(9-10): 629-31.
[http://dx.doi.org/10.1515/znc-2003-9-1004] [PMID: 14577620]
[24]
Ijaz H, Tulain UR, Qureshi J, et al. Review: Nigella sativa (prophetic medicine): a review. Pak J Pharm Sci 2017; 30(1): 229-34.
[PMID: 28603137]
[25]
Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 2001; 76(1): 45-8.
[http://dx.doi.org/10.1016/S0378-8741(01)00216-1] [PMID: 11378280]
[26]
Liu C, Zhou Q, Li Y, et al. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent Sci 2020; 6(3): 315-31.
[http://dx.doi.org/10.1021/acscentsci.0c00272] [PMID: 32226821]
[27]
Singh YKH. In silico identification and docking-based drug repurposing against the main protease of SARS-CoV-2, causative agent of COVID-19. ChemRxiv Prepr 2020; 2020: 1.
[28]
Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, et al. Structure-based drug design, virtual screening and high-throughput screening rapidly identify antiviral leads targeting COVID-19. bioRxiv 2020; 2020: 1.
[http://dx.doi.org/10.1101/2020.02.26.964882]]
[29]
Rappé AK, Casewit CJ, Colwell KS, Goddard WA, Skiff WM. UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. J Am Chem Soc 1992; 114(25): 10024-35.
[http://dx.doi.org/10.1021/ja00051a040]
[30]
Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Mol Biol 2015; 1263(1263): 243-50.
[http://dx.doi.org/10.1007/978-1-4939-2269-7_19] [PMID: 25618350]
[31]
Dassault Systèmes. Dassault systèmes BIOVIA, discovery studio modeling environment Available from: https://www.3dsbiovia. com/about/citations-references/2017
[32]
Molla S, Azad AK, Azam A, et al. A review on antiviral effects of Nigella sativa L. Pharmacol Online 2019; 2: 47-53.
[33]
Salem ML, Hossain MS. Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection. Int J Immunopharmacol 2000; 22(9): 729-40.
[http://dx.doi.org/10.1016/S0192-0561(00)00036-9] [PMID: 10884593]
[34]
Umar S, Tanveer M, Subhan S, et al. Protective and antiviral activities of Nigella sativa against avian influenza (H9N2) in turkeys. J Saudi Soc Agric Sci. J Saudi Soc Agric Sci 2016; 2016: 1-7.
[35]
Mohamed AH, Osman GY, Al-qormuti SA, Arabia S. Immunomodulatory and ameliorative role of Nigella sativa oil ON schistosoma mansoni infected mice. Can J Pure Appl Sci 2015; 9(2): 3345-55.
[36]
Aqil K, Khan M, Aslam A, et al. In vitro antiviral activity of Nigella sativa against Peste des Petits Ruminants (PPR) Virus. Pak J Zool 2018; 50(6): 2223-8.
[http://dx.doi.org/10.17582/journal.pjz/2018.50.6.2223.2228]
[37]
Mohamed EF. Inhibition of Broad Bean Mosaic Virus (BBMV) using extracts of Nigella (Nigella sativa L.) and Zizyphus (Zizyphus spina-christi Mill.) plants. J Am Sci 2011; 7(12): 727-34.
[38]
Onifade AA, Jewell AP, Adedeji WA. Nigella sativa concoction induced sustained seroreversion in HIV patient. Afr J Tradit Complement Altern Med 2013; 10(5): 332-5.
[http://dx.doi.org/10.4314/ajtcam.v10i5.18] [PMID: 24311845]
[39]
Oyero OG, Toyama M, Mitsuhiro N, et al. Selective inhibition of Hepatitis C virus replication by alpha-zam, a Nigella sativa seed formulation. Afr J Tradit Complement Altern Med 2016; 13(6): 144-8.
[http://dx.doi.org/10.21010/ajtcam.v13i6.20] [PMID: 28480371]
[40]
Elbeshehy EKF. Inhibitor activity of different medicinal plants extracts from Thuja orientalis, Nigella sativa L., Azadirachta indica and Bougainvillea spectabilis against Zucchini yellow mosaic virus (ZYMV) infecting Citrullus lanatus. Biotechnol Biotechnol Equip 2017; 31(2): 270-9.
[http://dx.doi.org/10.1080/13102818.2017.1279572]]
[41]
Maurya S, Marimuthu P, Singh A, Rao GP, Gurdip S. Antiviral activity of essential oils and acetone extracts of medicinal plants against papaya ring spot virus. J Essent Oil Bear Plants 2013; 8(3): 233-8.
[http://dx.doi.org/10.1080/0972060X.2005.10643452]
[42]
Yazdany J, Kim AHJ. Use of Hydroxychloroquine and chloroquine during the COVID-19 pandemic: what every clinician should know. Ann Intern Med 2020; 172(11): 754-5..
[http://dx.doi.org/10.7326/M20-1334 ] [PMID: 32232419]