Thymoquinone against infectious diseases: Perspectives in recent pandemics and future therapeutics

Document Type : Review Article


1 Research Division of Nature Study Society of Bangladesh, Dhaka, Bangladesh

2 Division of Molecular Cancer, Red Green Research Center, Dhaka, Bangladesh

3 Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka, Bangladesh

4 The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China

5 Department of Biochemistry and Molecular Biology, Tejgaon College, National University, Dhaka, Bangladesh

6 Bachelor in Medicine and Surgery Program, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China

7 Department of Immunology, Health Science Center, Shenzhen, University, Shenzhen, Guangdong, China


The recent pandemics caused by coronavirus infections have become major challenges in 21st century human health. Scientists are struggling hard to develop a complete cure for infectious diseases, for example, drugs or vaccines against these deadly infectious diseases. We have searched papers on thymoquinone (TQ) and its effects on different infectious diseases in databases like Pubmed, Web of Science, Scopus, and Google Scholar, and reviewed them in this study. To date research suggests that natural products may become a potential therapeutic option for their prodigious anti-viral or anti-microbial effects on infectious diseases. TQ, a natural phytochemical from black seeds, is known for its health-beneficial activities against several diseases, including infections. It is evident from different in vitro and in vivo studies that TQ is effective against tuberculosis, influenza, dengue, Ebola, Zika, hepatitis, malaria, HIV, and even recent pandemics caused by severe acute respiratory syndrome of coronaviruses (SARS-CoV and SARS-CoV-2). In these cases, the molecular mechanism of TQ is partly clear but mostly obscure. In this review article, we have discussed the role of TQ against different infectious diseases, including COVID-19, and also critically reviewed the future use of TQ use to fight against infectious diseases.


1. Salam AM, Quave CL. Opportunities for plant natural products in infection control. Curr Opin Microbiol 2018; 45:189-194.
2. Kim KJ, Liu X, Komabayashi T, Jeong SI, Selli S. Natural products for infectious diseases. Evid Based Complement Alternat Med 2016; 9459047.
3. Wang H, Wang Z, Dong Y, Chang R, Xu C, Yu X, et al. Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China. Cell Discov 2020; 6:10.
4. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 2020; 5:536-544.
5. Ganjhu RK, Mudgal PP, Maity H, Dowarha D, Devadiga S, Nag S, et al. Herbal plants and plant preparations as remedial approach for viral diseases. Virusdisease 2015; 26:225-236.
6. Denaro M, Smeriglio A, Barreca D, De Francesco C, Occhiuto C, Milano G, et al. Antiviral activity of plants and their isolated bioactive compounds: An update. Phytother Res 2020; 34:742-768.
7. Khan MA, Tania M, Fu S, Fu J. Thymoquinone, as an anticancer molecule: from basic research to clinical investigation. Oncotarget 2017; 8:51907-51919.
8. Khan MA, Tania M, Wei C, Mei Z, Fu S, Cheng J, et al. Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition. Oncotarget 2015; 6:19580-19591.
9. Khan MA, Chen HC, Tania M, Zhang DZ. Anticancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med 2011; 8:226-232.
10. Yimer M, 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.
11. Tavakkoli A, Mahdian V, Razavi BM, Hosseinzadeh H. Review on clinical trials of black seed (Nigella sativa ) and its active constituent, thymoquinone. J Pharmacopuncture 2017; 20:179-193.
12. Khader M, Eckl PM. Thymoquinone: an emerging natural drug with a wide range of medical applications. Iran J Basic Med Sci 2014; 17:950-957.
13. Khan MA, Thymoquinone, a constituent of prophetic medicine-black seed, is a miracle therapeutic molecule against multiple diseases. Int J Health Sci (Qassim) 2019; 13:1-2.
14. Bouchentouf S, Missoum N. Identification of compounds from Nigella Sativa as new potential inhibitors of 2019 novel coronasvirus (Covid-19): Molecular docking study. ChemRxiv 2020.
15. Ahmad A, Rehman MU, Ahmad P, Alkharfy KM, Covid-19 and thymoquinone: Connecting the dots. Phytother Res 2020; 34:2786-2789.
16. Da Costa VG, Moreli ML, Saivish MV. The emergence of SARS, MERS and novel SARS-2 coronaviruses in the 21st century. Arch Virol 2020; 165:1517-1526.
17. Morens DM, Daszak P, Markel H, Taubenberger JK. Pandemic COVID-19 Joins History’s Pandemic Legion. mBio 2020; 11:e00812-e00820.
18. Çelik I, Saatçi E, Eyübo─člu AF. Emerging and reemerging respiratory viral infections up to Covid-19. Turki J Med Sci 2020; 50:557-562.
19. Vabret A, Dina J, Gouarin S, Petitjean J, Tripey V, Brouard J, Freymuth F. Human (non-severe acute respiratory syndrome) coronavirus infections in hospitalised children in France. J Paediatr Child Health 2008; 44:176-181.
20. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, et al.  SARS Working Group, A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003; 348:1953-1966.
21. World Health Organization, Global alert and response (GAR), Summary table of SARS cases by country, 1 November 2002–7. 2003; (accessed 27 December 2012).
22. Cheng VC, Chan JF, To KK, Yuen KY. Clinical management and infection control of SARS: lessons learned. Antiviral Res 2013; 100:407-419.
23. Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y, et al. From SARS to MERS, Thrusting Coronaviruses into the Spotlight. Viruses 2019; 11:59.
24. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier RAM. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012; 367:1814-1820.
25. Ithete NL, Stoffberg S, Corman VM, Cottontail VM, Richards LR, Schoeman MC, et al. Close relative of human Middle East respiratory syndrome coronavirus in bat, South Africa. Emerg Infect Dis 2013; 19:1697-1699.
26. World Health Organization. Middle East respiratory syndrome. MERS situation update January 2020. 2020; (accessed 27 December 2020).
27. Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G, Sourvinos G, Tsiodras S. Full-genome evolutionary analysis of the novel coronavirus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol 2020; 79:104212.
28. Siam MHB, Nishat NH, Ahmed A, Hossain MS. Stopping the COVID-19 Pandemic: A Review on the advances of diagnosis, treatment, and control measures. J Pathog 2020; 9121429
29. Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C, et al. Transmission of 2019-nCoV Infection from an asymptomatic contact in Germany. N Engl J Med 2020; 382:970-971.
30. To KKW, Tsang OTY, Yip CCY, Chan KH, Wu TC, Chan JMC, et al. Consistent detection of 2019 novel coronavirus in saliva. Clinical Infectious Diseases 2020; 71:841-843.
31. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005; 436:112-116.
32. Meyerholz DK, Lambertz AM, Jr. McCray PB. Dipeptidyl peptidase 4 distribution in the human respiratory tract: Implications for the middle east respiratory syndrome. Am J Pathol 2016; 186:78-86.
33. Widagdo W, Raj VS, Schipper D, Kolijn K, van Leenders GKLH, Bosch BJ, et al. Differential expression of the middle east respiratory syndrome coronavirus receptor in the upper respiratory tracts of humans and dromedary camels. J Virol 2016; 90:4838-4842.
34. Jaijyan DK, Liu J, Hai R, Zhu H. Emerging and reemerging human viral diseases. Ann Microbiol Res 2018; 2:31-44.
35. Menachery VD, Yount Jr. BL, Debbink K, Agnihothram S, Gralinski LE, Plante JA, et al. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nat Med 2015; 21:1508-1513.
36. Li J, Khan MA, Wei C, Cheng J, Chen H, Yang L, et al. Thymoquinone inhibits the migration and invasive characteristics of cervical cancer cells siha and caski in vitro by targeting epithelial to mesenchymal transition associated transcription factors Twist1 and Zeb1. Molecules 2017; 22:2105.
37. Khan MA, Tania M, Fu J. Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics. Drug discovery today 2019; 24:2315-2322.
38. Alexander HR, Syed Alwi SS, Yazan LS, Zakarial Ansar FH. Ong YS. Migration and proliferation effects of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) and thymoquinone (TQ) on in vitro wound healing models. Evid Based Complement Alternat Med 2019; 2019:9725738. 
39. Xu J, Liu J, Yue G, Sun M, Li J, Xiu X, et al. Therapeutic effect of the natural compounds baicalein and baicalin on autoimmune diseases. Mol Med Rep 2018; 18:1149-1154.
40. Nagi MN, Mansour MA. Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 2000; 41:283-289.
41. Goel S, Mishra P. Thymoquinone inhibits biofilm formation and has selective antibacterial activity due to ROS generation. Appl Microbiol Biotechnol 2018; 102:1955-1967.
42. Rathore C, Upadhyay N, Kaundal R, Dwivedi RP, Rahatekar S, John A, et al. Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs. Expert Opin Drug Deliv 2020; 17:237-253.
43. Oskouei Z, Akaberi M, Hosseinzadeh H. A glance at black cumin (Nigella sativa) and its active constituent, thymoquinone, in ischemia: a review. Iran J Basic Med Sci 2018; 21:1200-1209.
44. 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; 17:929-938.
45. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395:497-506.
46. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395:507-513.
47. Li G, He X, Zhang L, Ran Q, Wang J, Xiong A, et al. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. J Autoimmun 2020; 112:102463.
48. Shawon J, Akter Z, Hossen MM, Akter Y, Sayeed A, Junaid M, et al. Current landscape of natural products against coronaviruses: Perspectives in COVID-19 treatment and anti-viral mechanism. Curr Pharm Des 2020; 26:5241-5260.
49. Elfiky A. Natural products may interfere with SARS-CoV-2 attachment to the host cell. J Biomol Struct Dyn 2020; 1-10.
50. Jakhmola Mani R, Sehgal N, Dogra N, Saxena S, Pande Katare D. Deciphering underlying mechanism of Sars-CoV-2 infection in humans and revealing the therapeutic potential of bioactive constituents from Nigella sativa to combat COVID19: in-silico study. J Biomol Struct Dyn 2020;  1-13.
51. Rahman MT. Potential benefits of combination of Nigella sativa and Zn supplements to treat COVID-19. J Herb Med 2020; 23:100382.
52. Xu H, Liu B, Xiao Z, Zhou M, Ge L, Jia F, et al. Computational and experimental studies reveal that thymoquinone blocks the entry of coronaviruses into in vitro cells. Infect Dis Ther 2021; 1–12. Advance online publication.
53. Khan MA, Younus H. Potential implications of black seed and its principal constituent Thymoquinone in the treatment of COVID-19 patients. Curr Pharm Biotechnol 2020; 10.2174/1389201021999201110205048. Advance online publication.
54. Ulasli M, Gurses SA, Bayraktar R, Yumrutas O, Oztuzcu S, Igci M, et al. The effects of Nigella sativa (Ns), Anthemis hyaline (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family. Mol Biol Rep 2014; 41:1703-1711.
55. Islam MN, Hossain KS, Sarker PP, Ferdous J, Hannan MA, Rahman MM, et al. Revisiting pharmacological potentials of Nigella sativa seed: a promising option for COVID-19 prevention and cure. Phytother Res 2021; 35:1329-1344.
56. Honey & Nigella sativa trial against COVID-19. Identifier: NCT04347382. 2020;
57. Mahmud HA, Seo H, Kim S, Islam MI, Nam KW, Cho HD, et al. Thymoquinone (TQ) inhibits the replication of intracellular Mycobacterium tuberculosis in macrophages and modulates nitric oxide production. BMC Complement Altern Med 2017; 17:279.
58. Dehyab AS, Bakar MFA, Al-Omar MK, Sabran SF. A review of medicinal plant of Middle East and North Africa (MENA) region as source in tuberculosis drug discovery. Saudi J Biol Sci 2020: 27:2457-2478.
59. Randhawa MA. In vitro antituberculous activity of thymoquinone, an active principle of Nigella sativa. J Ayub Med Coll Abbottabad 2011; 23:78-81.
60. Dey D, Ray R, Hazra B. Antitubercular and antibacterial activity of quinonoid natural products against multi-drug resistant clinical isolates. Phytother Res 2014; 28:1014-1021.
61. Jaswal A, Sinha N, Bhadauria M, Shrivastava S, Shukla S. Therapeutic potential of thymoquinone against anti-tuberculosis drugs induced liver damage. Environ Toxicol Pharmacol 2013; 36:779-786.
62. Umar S, Munir MT, Subhan S, Azam T, Nisa Q, Khan MI, et al. Protective and antiviral activities of Nigella sativa against avian influenza (H9N2) in turkeys. J Saudi Soci Agri Sci 2016; In press.
63. World Health Organization. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. Geneva 1997; 2nd edition: Available at: Extracted on December 29, 2020.
64. Saleem HN, Batool F, Mansoor HJ, Shahzad-ul-Hussan S, Saeed M. Inhibition of dengue virus protease by eugeniin, isobiflorin, and biflorin isolated from the flower buds of syzygium aromaticum (Cloves). ACS Omega 2019; 4:1525-1533.
65. Ahmed AM, Al-Olayan EM, Aboul-Soud MAM, Al-Khedhairy AA. The immune enhancer, thymoquinone, and the hope of utilizing the immune system of Aedes caspius against disease agents. Afr J Biotechnol 2010; 9:3183-3195.
66. Sayed SME, Abdelrahman AA, Ozbak HA, Hemeg HA, Kheyami AM, Rezk N, et al. Updates in diagnosis and management of Ebola hemorrhagic fever. J Res Med Sci 2016; 21:1-27.
67. Uzochukwu IC, Olubiyi OO, Ezebuo FC, Obinwa IC, Ajaegbu EE, Eze PM, et al. Ending the Ebola Virus Scourge: A case for natural products. J Pharm Res 2016; 1:000105.
68. United Nations Development Group (UNDG) – Western and Central Africa, Socio-Economic Impact of Ebola Virus Disease in West African Countries: A call for national and regional containment, recovery and prevention, (2015) Available at: (Extracted on December 29, 2020)
69. Elfiky AA. Novel guanosine derivatives against Zika virus polymerase in silico. J Med Virol 2020; 92:11-16.
70. World Health Organization,  European Region, Zika virus technical report: Interim Risk Assessment, (2016) Available at: (Extracted on December 29, 2020)
71. Cirne-Santos CC, Barros CDS, Paixão ICNP. Natural Products against the Zika Virus. Am. J Biomed Sci Res 2020; 7:001146.
72. Te HS, Jensen DM. Epidemiology of hepatitis B and C viruses: A global overview. Clin Liver Dis 2010; 1-21.
73. Jefferies M, Rauff B, Rashid H, Lam T, Rafiq S. Update on global epidemiology of viral hepatitis and preventive strategies. World J Clin Cases 2018; 6:589-599.
74. Barakat EMF, Wakeel LME, Hagag RS. Effects of Nigella sativa on outcome of hepatitis C in Egypt. World J Gastroenterol 2013; 19:2529-2536.
75. Khan MA. Antimicrobial Action of Thymoquinone, Hina Younus (Ed), Molecular and Therapeutic actions of Thymoquinone. Springer Nature Singapore Pte Ltd; 2018.p. 57-64.
76. Noorbakhsh MF, Hayati F, Samarghandian S, Shaterzadeh-Yazdi H, Farkhondeh T. An Overview of hepatoprotective effects of thymoquinone. Recent Pat Food Nutr Agric 2018; 9:14-22.
77. Abdel-Moneim A, Morsy BM, Mahmoud AM, Abo-Seif MA, Zanaty MI. Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egypt. EXCLI J 2013; 12:943-955.
78. World Health Organization (WHO). World malaria report 2020: 20 years of global progress and challenges. 2020; (Extract on January 1, 2020).
79. Autino B, Noris A, Russo R, Castelli F. Epidemiology of malaria in endemic areas. Mediterr J Hematol Infect Dis 2012; 4:e2012060.
80. Ashcroft OF, Salaudeen OF, Mohammed K, Spencer THI, Garba MK, Nataala SU, et al. Anti-malarial effect of Nigella Sativa seeds (Black seed) extract on mice infected with plasmodium bergei (NK 65). Eur J Pharm  Med Res 2018; 5:131-137.
81. Fröhlich T, Reiter C, Saeed MEM, Hutterer C, Hahn F, Leidenberger M, et al. Synthesis of thymoquinone–artemisinin hybrids: New potent antileukemia, antiviral, and antimalarial agents. ACS Med Chem Lett 2018; 9:534-539.
82. Johnson-Ajinwo OR, Ullah I, Mbye H, Richardson A, Horrocks P, Li WW. The synthesis and evaluation of thymoquinone analogues as anti-ovarian cancer and antimalarial agents. Bioorg Med Chem Lett 2018; 28(7):1219-1222.
83. Emeka PM, Badger-Emeka LI, Eneh CM, Khan TM. Dietary supplementation of chloroquine with Nigella sativa seed and oil extracts in the treatment of malaria induced in mice with Plasmodium berghei. Pharmacogn Mag 2014; 10:S357-S362.
84. World Health Organization (WHO). HIV/AIDS; Key facts. 2019; (Extract on January 1, 2020)
85. United Nations Programme on HIV/AIDS (UNAIDS). Global HIV & AIDS statistics-2020 fact sheet. 2020;,AIDS%2Drelated%20illnesses%20in%202019. (Extracted on January 1, 2021).
86. Chandra S, Mondal D, Agrawal KC. HIV-1 protease inhibitor induced oxidative stress suppresses glucose stimulated insulin release: protection with thymoquinone. Exp Biol Med (Maywood) 2009; 234(4):442-453.
87. Onifade A, Jewell A, Ajadi T, Rahamon S, Ogunrin, O. Effectiveness of a herbal remedy in six HIV patients in Nigeria. J Herb Med 2013; 3:99-103.
88. Onifade AA, Jewell AP, Okesina AB. Virologic and immunologic outcomes of treatment of HIV infection with herbal concoction, A-zam among clients seeking herbal remedy in Nigeria. Afr J Tradit Complement Altern Med 2011; 8:37-44.
89. Onifade AA, Jewell AP, Okesina AB. Seronegative conversion of an HIV positive subject treated with Nigella sativa and honey. Afr J Infect Dis 2015; 9:47-50.
90. Onifade AA, Jewell AP, Adedeji WA. Nigella Sativa concoction induced sustained seroreversion in HIV patient. Afr J Tradit Complement Altern Med 2013; 10:332-335.
91. Negi P, Rathore C, Sharma G, Singh B, Katare OP. Thymoquinone a potential therapeutic molecule from the plant Nigella sativa: Role of colloidal carriers in its effective delivery. Recent Pat Drug Deliv Formul 2018; 12:3-22.
92. Gupta SK, Nayak RP. Dry antibiotic pipeline: Regulatory bottlenecks and regulatory reforms. J Pharmacol Pharmacother 2014; 5:4-7.
93. Elmowafy M, Samy A, Raslan MA, Salama A, Said RA, Abdelaziz AE, et al. Enhancement of Bioavailability and pharmacodynamic effects of thymoquinone via nanostructured lipid carrier (NLC) formulation. AAPS PharmSciTech 2016; 17:663-672.