Black seeds (Nigella sativa) for the management of dengue viral disease: insight into the evidence and POM analyses for the identification of antiviral pharmacophore sites: a review

Subject Areas : Journal of Medicinal Herbs, "J. Med Herb" (Formerly known as Journal of Herbal Drugs or J. Herb Drug)

Naina Mohamed Pakkir Maideen ¹ , Taibi Ben Hadda ² , Faisal Almalki ³ , Hamid Laarousi ⁴ , Sameh Soliman ⁵ , Sarkar Kawsar ⁶

1 - Pharmacologist, Dubai Health Authority, Dubai, UAE
2 - Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Université Mohamed Premier, BV Mohammed VI BP 717 60000, Oujda, Morocco
3 - Umm Al-Qura University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Makkah Almukkarramah 21955, Saudi Arabia
4 - Mohammed Premier University, Faculty of Science, Laboratory of Applied Chemistry & Environment, BP 524, Oujda 60000 , Morocco
5 - Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
6 - Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh

Received: 2022-10-20 Accepted : 2023-02-25 Published : 2023-05-22

Keywords: Nigella sativa, Thymoquinone, Black seeds, Dengue virus infection, POM (Petra/Osiris/Molinspiration) theory, Identification of antiviral pharmacophore site,

Abstract :

Background & Aim: The number of dengue virus (DENV) infection cases has increased dramatically over the past two decades, with an estimated 3.9 billion cases across the globe potentially at risk. Patients with a DENV infection are managed symptomatically and by supportive care since there is no approved antiviral drug yet for its management. On the other hand, N. sativa has been highlighted as a potential antiviral, particularly against DENV.Experimental: Hence, the anti-DENV potential of N. sativa is analyzed in this review using major databases, including Medline/PMC/PubMed, Scopus, EBSCO, EMBASE, Google Scholar, and Science Direct. Moreover, the Petra/Osiris/Molinspiration (POM) bioinformatics platform-2019 was used to analyze a series of compounds (1-15) identified in N. sativa (black seeds) to identify those with promising antiviral pharmacophore sites.Results: Preliminary research showed the potential of N. sativa in the control of Aedes aegypti mosquitoes and the enhancement of platelet counts. In addition, several clinical, animal, in vitro and in vivo studies have demonstrated the antiviral, immunomodulatory and anti-inflammatory properties of N. sativa. Furthermore, calculation of the physico-chemical properties of N. sativa compounds using POM analyses indicated that dithymoquinone possesses potential antiviral activity with two (O, O’) pharmacophore sites.Recommended applications/industries: As a result, N. sativa can be employed as an adjuvant/supportive therapy in the management of DENV infection in the early stages of the illness. Furthermore, N. sativa can be a source of new lead anti-DENV drugs.

References:

Abdel-Sater, K.A. 2009. Gastroprotective effects of Nigella sativa oil on the formation of stress gastritis in hypothyroidal rats. International Journal of Physiology, Pathophysiology and Pharmacology, 1(2):143-149.
Adam, G.O., Rahman, M.M., Lee, S.J., Kim, G.B., Kang, H.S., Kim, J.S. and Kim, S.J. 2016. Hepatoprotective effects of Nigella sativa seed extract against acetaminophen-induced oxidative stress. Asian Pacific Journal of Tropical Medicine, 9(3):221-227.
Ahmed, A.M., Al-Olayan, E.M. and Amoudy, M.A. 2008. Enhancing the humoral and melanization responses of Aedes aegypti mosquito: A step toward the utilization of immune. Journal of Entomology, 5(5):305-321.
Ahmed, A.M., Al-Olayan, E.M., Aboul-Soud, M.A. and Al-Khedhairy, A.A. 2010. The immune enhancer, thymoquinone, and the hope of utilizing the immune system of Aedes caspius against disease agents. African Journal of Biotechnology, 9(21):3183-3195.
Ajlan, B.A., Alafif, M.M., Alawi, M.M., Akbar, N.A., Aldigs, E.K. and Madani, T.A. 2019. Assessment of the new World Health Organization's dengue classification for predicting severity of illness and level of healthcare needed. PLoS Neglected Tropical Diseases, 13(8):e0007144.
Aktaş, İ. and Mehmet, G.F. 2021. Hepato-protective effects of thymoquinone and beta-aminoisobutyric acid in streptozocin induced diabetic rats. Biotechnic and Histochemistry, 97(1):67-76.
Alhibshi, A.H., Odawara, A. and Suzuki, I. 2019. Neuroprotective efficacy of thymoquinone against amyloid beta-induced neurotoxicity in human induced pluripotent stem cell-derived cholinergic neurons. Biochemistry and Biophysics Reports, 17:122-126.
Al-Maqtari, H.M., Jamalis, J., Hadda, T.B., Sankaranarayanan, M., Chander, S., Ahmad, N.A., Sirat, H.M., Althagafi, II. and Mabkhot, Y.N. 2017. Synthesis, characterization, POM analysis and antifungal activity of novel heterocyclic chalcone derivatives containing acylated pyrazole. Research on Chemical Intermediates, 43:1893-1907.
Azizi,, F., Ghorat, F., Rakhshani, M.H. and Rad, M. 2019. Comparison of the effect of topical use of Nigella sativa oil and diclofenac gel on osteoarthritis pain in older people: A randomized, double-blind, clinical trial. Journal of Herbal Medicine, 16:100259.
Berger, A., 2000. Th1 and Th2 responses: what are they? British Medical Journal, 321:424.
Bhat, A.R., Dreong, R.S., Almalki, F.A., Berredjem, M., Aissaoui, M., Touzani, R. and Hadda, T.B. 2021. Synthesis, biological activity and POM/DFT/Docking analyses of annulated pyrano[2,3-d]pyrimidine derivatives: Identification of antibacterial and antitumor pharmacophore sites. Bioorganic Chemistry, 106:104480
Bhatt, P., Sabeena S.P., Varma, M. and Arunkumar, G. 2021. Current understanding of the pathogenesis of dengue virus infection. Current Microbiology, 78:17-32.
Bhat, A.R., Dongre, R.S., Hadda, T.B., Almalki, F.A., Rastija, V., Karnas, M., Laaroussi, H., Moueqqit, M., Nath, M.A. and Kawsar, S.M.A. 2023. Eco-friendly synthesis, antibacterial and antifungal activity evaluation of some new thiazolidine (TZD) derivatives: DFT/POM analyses for identification of pharmacophore sites. Journal of Biomolecular Structure and Dynamics, 41.
Boo, Y.L., Lim, S.Y., P'ng, H.S., Liam, C.C. and Huan, N.C. 2019. Persistent thrombocytopenia following dengue fever: What should we do?. Malaysian family physician: Malaysian Family Physician, 14:71-73.
Bordoni, L., Fedeli, D., Nasuti, C., Maggi, F., Papa, F., Wabitsch, M., De Caterina, R. and Gabbianelli, R. 2019. Antioxidant and anti-inflammatory properties of Nigella sativa oil in human preadipocytes. Antioxidants, 8:51.
Cardenas, J.C., Giraldo-Parra, S.Y., Gonzalez, M.U., Gutierrez-Silva, L.Y., Jaimes-Villamizar, L., Roa-Parra, A.L., Carvajal, D.J., Valdivia, H.O., Sanchez, J.F., Colpitts, T.M. and Londono-Renteria, B. 2021. Laboratory findings in patients with probable dengue diagnosis from an endemic area in Colombia in 2018. Viruses, 13:1401.
Carod-Artal, F.J. 2019. Neurological complications associated with dengue virus infection. Revista de Neurologia, 69:113-122.
Cascella, M., Palma, G., Barbieri, A., Bimonte, S., Amruthraj, N.J., Muzio, M.R., Del Vecchio, V., Rea, D., Falco, M., Luciano, A. and Arra, C. 2017. Role of Nigella sativa and its constituent thymoquinone on chemotherapy-induced nephrotoxicity: evidence from experimental animal studies. Nutrients, 9(6):625.
Castillo, J.A., Naranjo, J.S., Rojas, M., Castaño, D. and Velilla, P.A. 2019. Role of monocytes in the pathogenesis of dengue. Archivum Immunologiae et Therapiae Experimentals, 67:27-40.
Chen, C.H., Huang, Y.C., Kuo, K.C. and Li, .CC. 2018. Clinical features and dynamic ordinary laboratory tests differentiating dengue fever from other febrile illnesses in children. Journal of Microbiology, Immunology and Infection, 51:614-620.
Chew, M.F., Poh, K.S. and Poh, C.L. 2017. Peptides as therapeutic agents for dengue virus. International Journal of Medical Sciences, 14:1342-1359.
Dera, A.A., Rajagopalan, P., Alfhili, M.A., Ahmed, I. and Chandramoorthy, H.C. 2020. Thymoquinone attenuates oxidative stress of kidney mitochondria and exerts nephroprotective effects in oxonic acid-induced hyperuricemia rats. Biofactors, 46:292-300.
Dissanayake, H.A. and Seneviratne, S.L. 2018. Liver involvement in dengue viral infections. Reviews in Medical Virology, 28:e1971.
Dongre, R.S., Meshram, J.S., Selokar, R.S., Almalki, F.A. and Hadda, T.B. 2018. Antibacterial activity of synthetic pyrido[2,3-d]pyrimidines armed with nitrile group: POM analyses and identification of pharmacophore sites of nitriles as important pro-drugs. New Journal of Chemistry, 42:15610-15617.
El-Shanshory, M., Hablas, N.M., Aboonq M.S., Fakhreldin, A.R., Attia, M., Arafa, W., Mariah, R.A., Baghdadi, H., Ayat, M., Zolaly, M. and Nabo, M.M. 2019. Nigella sativa improves anemia, enhances immunity and relieves iron overload-induced oxidative stress as a novel promising treatment in children having beta-thalassemia major. Journal of Herbal Medicine, 16:100245.
Erboga, M., Kanter, M., Aktas, C., Sener, U., Erboga, Z.F., Donmez, Y.B. and Gurel, A. 2016. Thymoquinone ameliorates cadmium-induced nephrotoxicity, apoptosis, and oxidative stress in rats is based on its anti-apoptotic and antioxidant properties. Biological Trace Element Research, 170:165-172
Esharkawy, E.R., Almalki, F.A. and Hadda, T.B. 2022. In vitro potential antiviral SARS-CoV-19- activity of natural product thymohydroquinone and dithymoquinone from Nigella sativa. Bioorganic Chemistry, 120:105587.
Eswarappa, M., Reddy, S.B., John, M.M., Suryadevara, S. and Madhyashatha, R.P. 2019. Renal manifestations of dengue viral infection. Saudi Journal of Kidney Diseases and Transplantation, 30:394-400.
Fahma, Wijayanti, Moh, N. and Ibnu, S. 2019. Analysis of black seed effect on Aedes aegypti. International Journal of Zoological Research, 15:13-20.
Farkhondeh, T., Samarghandian, S., Borji, A. 2017. An overview on cardioprotective and anti-diabetic effects of thymoquinone. Asian Pacific Journal of Tropical Medicine, 10:849-854.
Farkhondeh, T., Samarghandian, S., Shahri, A.M. and Samini, F. 2018. The neuroprotective effects of thymoquinone: A review. Dose‒Response, 16:1559325818761455.
Ferreira-de-Lima, V.H. and Lima-Camara, T.N. 2018. Natural vertical transmission of dengue virus in Aedes aegypti and Aedes albopictus: a systematic review. Parasites and Vectors, 11:77.
Gheita, T.A. and Kenawy, S.A. 2012. Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled study. Phytotherapy Research, 26:1246-1248.
Glasner, D.R., Puerta-Guardo, H., Beatty, P.R. and Harris, E. 2018. The good, the bad, and the shocking: the multiple roles of dengue virus nonstructural protein 1 in protection and pathogenesis. Annual Review of Virology, 5:227-253.
Grib, I., Berredjem, M., Rachedi, K.O., Djouad, S.E., Bouacida, S., Bahadi, R., Ouk, T.S., Kadri, M. and Hadda, T.B. 2020. Novel N-sulfonylphthalimides: Efficient synthesis, X-ray characterization, spectral investigations, POM analyses, DFT computations and antibacterial activity. Journal of Molecular Structure, 1217:128423.
Gurugama, P., Jayarajah, U., Wanigasuriya, K., Wijewickrama, A., Perera, J. and Seneviratne, S.L. 2018. Renal manifestations of dengue virus infections. Journal of Clinical Virology, 101:1-6.
Hadda, T.B., Rastija, V., AlMalki, F., Titi, A., Touzani, R., Mabkhot, Y.N., Khalid, S., Zarrouk, A. and Siddiqui, B.S. 2021. Petra/Osiris/Molinspiration and molecular docking analyses of 3-hydroxy-indolin-2-one derivatives as potential antiviral agents. Current Computer-Aided Drug Design, 17(1):123-133.
Hadda, T.B., Berredjem, M., AlMalki, F.A., Rastija, V., Jamalis, J., Bin Emran T., Abu-Izneid, T., Esharkawy, E., Rodriguez, L.C. and Alqahtani, A.M. 2021. How to face COVID-19: proposed treatments based on Remdesivir and hydroxychloroquine in the presence of zinc sulfate. Docking/DFT/POM structural analysis. Journal of Biomolecular Structure and Dynamics, 25:1-14.
Hadinegoro, S.R. 2012. The revised WHO dengue case classification: does the system need to be modified? Pediatrics and International Child Health, 32:33-38.
Hadi, V., Kheirouri, S., Alizadeh, M., Khabbazi, A. and Hosseini, H. 2016. Effects of Nigella sativa oil extract on inflammatory cytokine response and oxidative stress status in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial. Avicenna Journal of Phytomedicine, 6:34-43.
Halstead, S. 2019. Recent advances in understanding dengue. F1000Res 8: F1000 Faculty Rev-1279.
Htun, T.P., Xiong, Z. and Pang, J. 2021. Clinical signs and symptoms associated with WHO severe dengue classification: A systematic review and meta-analysis. Emerging Microbes and Infections. 10:1116-1128.
Hosen, M.A., Munia, N.S., Al-Ghorbani, M., Baashen, M., Almalki, F.A., Hadda, T.B., Ali, F., Mahmud, S., Saleh, M.A., Laaroussi, H. and Kawsar, S.M.A. 2022. Synthesis, antimicrobial, molecular docking and molecular dynamics studies of lauroyl thymidine analogs against SARS-CoV-2: POM study and identification of the pharmacophore sites. Bioorganic Chemistry, 125:105850.
Hosen, M.I., Mukhrish, Y.E., Jawhari, A.H., Celik, I., Erol, M., Abdallah, E.M., Al-Ghorbani, M., Baashen, M., Almalki, F.A., Laaroussi, H., Hadda, T.B. and Kawsar, S.M.A. 2023a. Design, synthesis, in silico and POM studies for the identification of the pharmacophore sites of benzylidene derivatives. Molecules, 28:2613.
Hosen, M.A., Qais, F.A., Chtita, S., Rahman, I.A., Almehdi, A.M., Ali, F., Almalki, F.A., Hadda, T.B., Laaroussi, H. and Kawsar, S.M.A. 2023. In silico and POM analysis for potential antimicrobial agents of thymidine analogs by using molecular docking, molecular dynamics and ADMET profiling. Nucleosides Nucleotides & Nucleic Acids, 42.
John, A.L. and Rathore, A.P. 2019. Adaptive immune responses to primary and secondary dengue virus infections. Nature Reviewes Immunology, 19:218-230.
Kanter, M., Demir, H., Karakaya, C. and Ozbek, H. 2005. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World Journal of Gastroenterology, 11:6662-6666.
Kao, Y.T., Lai, M. and Yu, C.Y. 2018. How dengue virus circumvents innate immunity. Frontiers in Immunology, 9:2860.
Khana, H., Khana, Z., Aminb, S., Mabkhot, Y.N., Mubarak, M.S., Hadda, T.B. and Maionef, F. 2017. PLant bioactive molecules bearing glycosides as lead compounds for the treatment of fungal infection: A review. Biomedicine and Pharmacotherapy, 93:498-509.
Kheirouri, S., Hadi, V. and Alizadeh, M. 2016. Immunomodulatory effect of Nigella sativa oil on T lymphocytes in patients with rheumatoid arthritis. Immunological Investigations 45:271-283.
Kawsar, S.M.A., Almalki, F.A., Hadda, T.B., Laaroussi, H., Khan, M.A.R., Hosen, M.A., Mahmud, S., Aounti, A., Maideen, N.M.P., Heidarizadeh, F.and Soliman, S.S.M. 2023. Potential antifungal activity of novel carbohydrate derivatives validated by POM, molecular docking and molecular dynamic simulations analyses. Molecular Simulation, 49:60-75.
Kawsar, S.M.A., Hosen, M.A., Ahmad, S., Bakri, Y.E., Laaroussi, H., Hadda, T.B., Almalki, F.A., Ozeki, Y., Goumri-Said, S. 2022. Potential SARS-CoV-2 RdRp inhibitors of cytidine derivatives: molecular docking, molecular dynamic simulations, ADMET, and POM analyses for the identification of pharmacophore sites. PLoS ONE, 17: e0273256.
Kawsar, S.M.A., Mamun, S.M.A., Rahman, M.S., Yasumitsu, H. and Ozeki, Y. 2010a. Growth inhibitory effects of a GlcNAc/GalNAc-specific lectin from the marine demosponge Halichondria okadai on human pathogenic microorganisms. Journal of Cell and Molecular Biology, 8:65-75.
Kawsar, S.M.A., Sheikh A., Yasumitsu, H. and Ozeki, Y. 2010b. The cytotoxic activity of two D-galactose-binding lectins purified from marine invertebrates. Archives of Biological Sciences, 62:1027-1034.
Kawsar, S.M.A., Golam M., Enamul H., Nilufar N. and Ozeki, Y. 2009. Chemical constituents and hemolytic activity of Macrotyloma uniflorum L. International Journal of Biological Chemistry, 3:42-28.
Kawsar, S.M.A., Huq E. and Nahar N. 2008a. Cytotoxicity assessment of the aerial parts of Macrotyloma uniflorum Linn. International Journal of Pharmacology, 4:297-300.
Kawsar, S.M.A., Uddin, M.S., Huq, E., Nahar, N., Ozeki, Y. 2008b. Biological investigation of Macrotyloma uniflorum Linn extracts against some pathogens. Journal of Biological Sciences, 8:1051-1056.
Kawsar, S.M.A., Huq, E., Nahar, N. and Ozeki, Y. 2008c. Identification and quantification of phenolic acids in Macrotyloma uniflorum by reversed phase-HPLC. American Journal of Plant Physiology, 3:165-172.
Lafridi, H., Almalki, F.A., Hadda, T.B., Berredjem, M., Kawsar, S.M.A., Alqahtani, A.M., Esharkawy, E., Lakhrissi, B. and Zgou, H. 2023. In silico evaluation of molecular interactions between macrocyclic inhibitors with the HCV NS3 protease. Docking and identification of antiviral pharmacophore site. Journal of Biomolecular Structure and Dynamics, 41:2260-2273.
Lai, Y.C., Chao, C.H. and Yeh, T.M. 2020. Roles of macrophage migration inhibitory factor in Dengue pathogenesis: from pathogenic factor to therapeutic target. Microorganisms, 8:891.
Li, G.H., Ning, Z.J., Liu, Y.M. and Li, X.H. 2017. Neurological manifestations of dengue infection. Frontiers in Cellular and Infection Microbiology, 7: 449.
Mahdy, A. and Gheita, T. 2009. Beneficial effects of Nigella sativa seed oil as adjunct therapy in rheumatoid arthritis. Journal of the Egyptian Society of Toxicology, 41:31-37.
Maideen, N.M. 2020. Prophetic medicine- Nigella sativa (black cumin seeds)–potential herb for COVID-19? Journal of Pharmacopunct 23:62-70.
Maideen, N.M. 2021a. Antidiabetic activity of Nigella sativa (black seeds) and its active constituent (Thymoquinone): A review of human and experimental animal studies. Chonnam Medical Journal, 57:169-175.
Maideen, N.M., Balasubramanian, R. and Ramanathan, S. 2021b. Nigella sativa (black seeds), a potential herb for the pharmacotherapeutic management of hypertension-A review. Current Cardiology Review, 17:7-13.
Maideen, N.M. 2021c. Effects of Nigella sativa (black seeds) supplementation on plasma lipid profile in human subjects- A review. Current Nutraceuticals, e021221198487.
Maideen, N.M. 2021d. Nigella sativa (black seeds)-potential herb to help weight loss. Current Traditinal Medicine, e091121197833.
Maideen, P. and Mohamed, N. 2021. Miracle herb to cure HIV-black seeds (Nigella sativa): A review. International Journal of Medical Review, 8:116-121.
Malavige, G.N., Jeewandara, C. and Ogg, G.S. 2020. Dysfunctional innate immune responses and severe dengue. Frontiers Cellular Infections Microbiology, 10:600.
Matsumoto, R., Shibata, T.F., Kohtsuka, H., Sekifuji, M., Sugii, N., Nakajima, H., Kojima, N., Fujii, Y., Kawsar, S.M.A., Yasumitsu, H., Hamako, J., Matsui, T. and Ozeki, Y. 2011. Glycomics of a novel type-2 N-acetyllactosamine-specific lectin purified from the feather star, Oxycomanthus japonicus (Pelmatozoa: Crinoidea). Comparative Biochemistry and Physiology, 158B:266-273.
Muller, D.A., Depelsenaire, A.C. and Young, P.R. 2017. Clinical and laboratory diagnosis of dengue virus infection. The Journal of Infectious Diseases, 215:S89-95.
Murugesan, A. and Manoharan, M. 2019. Dengue virus. Emerg reemerg viral pathogens, Elsevier, Academic Press.
Naaraayan, S.A. and Sundar, K.C. 2021. Risk factors for severe dengue in children: A nested case‒control study. Journal of Pediatric Critical Care, 8:224.
Nanaware, N., Banerjee, A., Mullick, B.S., Bagchi, P. and Mukherjee, A. 2021. Dengue virus infection: A tale of viral exploitations and host responses. Viruses, 13:1967.
Nasar, S., Rashid, N.and Iftikhar, S. 2020. Dengue proteins with their role in pathogenesis, and strategies for developing an effective anti‐dengue treatment: A review. Journal of Medical Virology, 92: 941-955.
Munia, N.S., Hosen, M.A., Azzam, K.M.A., Al-Ghorbani, M., Baashen, M., Hossain, M.K., Ali, F., Mahmud, S., Shimu, M.S.S., Almalk, F.A., Hadda, T.B., Laaroussi, H., Naimi, S. and Kawsar, S.M.A. 2022. Synthesis, antimicrobial, SAR, PASS, molecular docking, molecular dynamics and pharmacokinetics studies of 5´-O-uridine derivatives bearing acyl moieties: POM study and identification of the pharmacophore sites. Nucleosides Nucleotides Nucleic Acids, 41:2096898.
Niu, C., Huang, Y., Wang, M., Huang, D., Li J., Huang, S., Yang, F., Wan, C. and Zhang, R. 2020. Differences in the transmission of Dengue fever by different serotypes of Dengue virus. Vector-Borne Zoonotic Diseases, 20:143-150.
Niu, Y., Wang, B., Zhou, L., Ma C., Waterhouse, G.I., Liu Z., Ahmed, A.F., Sun-Waterhouse, D., Kang, W. 2021. Nigella sativa: A Dietary supplement as an immune-modulator on the basis of bioactive components. Frontiers Nutrition, 64:521.
Noorbakhsh, M.F., Hayati, F., Samarghandian, S., Shaterzadeh-Yazdi, H., Farkhondeh, T. 2018. An overview of hepatoprotective effects of thymoquinone. Recent Patents on Food, Nutrition & Agriculture, 9:14-22.
Obi, J.O., Barbosa, H.G., Chua, J.V. and Deredge, D.J. 2021. Tropical medicine and infectious disease review current trends and limitations in Dengue antiviral research. Tropical Medicicnal Infections Diseases, 6:180.
Ostadpoor, M. and Gholami-Ahangaran, M. 2021. A review on hepatoprotective effects of Nigella sativa L. Journal of Medicinal Herbs, 12:49-54.
Pakkir, M.N.M. 2021. Potential of black seeds (Nigella sativa) in the management of COVID-19 among children. International Journal of Medical Device and Adjuvant Treatments,4:e366.
Patra, G., Saha, B. and Mukhopadhyay, S. 2021. Increased levels of pentraxins protein and cytokines bear good association in patients with severe dengue infection. Science Report, 11:511.
Rbaa, M., Hichar, A., Dohare, P., Anouar, H., Lakhrissi, Y., Lakhrissi, B., Berredjem, M., Almalki, F., Rastija, V., Rajabi, M., Hadda, T.B. Zarrou, A. 2021. Synthesis, characterization, biocomputational modeling and antibacterial study of novel pyran based on 8-hydroxyquinoline. Arab Journal of Science and Engineering, 46:5533–5542.
Raj, G.A., Chandrasekaran, M., Krishnamoorthy, S., Jayaraman, M. and Venkatesalu, V. 2015. Phytochemical profile and larvicidal properties of seed essential oil from Nigella sativa L. (Ranunculaceae), against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus (Diptera: Culicidae). Parasitol Research, 114:3385-3391.
Ran, J., Xu, H. and Li, W. 2021. Cardioprotective effects of coadministration of thymoquinone and ischemic postconditioning in diabetic rats. Iranian Journal of Basic Medical Sciences, 24:892-99.
Rather, I.A., Parray, H.A., Lone, J.B., Paek, W.K., Lim, J., Bajpai, V.K. and Park, Y.H. 2017. Prevention and control strategies to counter dengue virus infection. Front Cell Infect Microbiol 7:336.
Rathore, A.P., Mantri, C.K., Tan, M.W., Shirazi, R., Nishida, A., Aman, S.A., Morrison, J. St John, A.L. 2021. Immunological and pathological landscape of Dengue serotypes 1-4 infections in immune-competent mice. Frontiers Immunology, 12: 2133.
Reddy, S.B., Chin, W.X. Shivananju, N.S. 2018. Dengue virus NS2 and NS4: Minor proteins, mammoth roles. Biochemistry Pharmacology, 154: 54-63.
Salehi, B., Quispe, C., Imran, M., Ul-Haq, I., Živković, J., Abu-Reidah, I.M., Sen, S., Taheri, Y., Acharya, K., Azadi, H. and del Mar Contreras, M. 2021. Nigella plants–traditional uses, bioactive phytoconstituents, preclinical and clinical studies. Frontiers Pharmacology, 12:625386.
Saadia, M., Rehman, S., Robin, S., Ruby, T., Sher, M., Siddiqui, W.A. and Khan, M.A. 2017. Potential of Nigella sativa seed aqueous extract in ameliorating quinine-induced thrombocytopenia in rats. Pakistan Journal of Pharmaceutical Sciences, 30:1679-1690.
Sangkaew, S., Ming, D., Boonyasiri, A., Honeyford, K., Kalayanarooj, S., Yacoub, S., Dorigatti, I.and Holmes, A. 2021. Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis. Lancet Infectious Diseases, 21:1014-26.
Shrivastava, G., Visoso-Carvajal, G., Garcia-Cordero, J., Leon-Juarez, M., Chavez-Munguia, B. and Lopez, T., Nava, P., Villegas-Sepulveda, N., Cedillo-Barron, L. 2020. Dengue virus serotype 2 and its nonstructural proteins 2A and 2B activate NLRP3 inflammasome. Frontiers Immunology, 11:352.
Shukla, R., Ramasamy, V., Shanmugam, R.K., Ahuja, R. and Khanna, N. 2020. Antibody-dependent enhancement: A challenge for developing a safe dengue vaccine. Frontiers in Cellular Infections Microbiology, 10:572681.
Somkijrungroj, T. and Kongwattananon, W. 2019. Ocular manifestations of dengue. Current Opinion Ophthalmology, 30:500-505.
Tremblay, N., Freppel, W., Sow, A.A. and Chatel-Chaix, L. 2019. The interplay between dengue virus and the human innate immune system: A game of hide and seek. Vaccines, 7:145.
Tay, M.Y. and Vasudevan, S.G. 2018. The transactions of NS3 and NS5 in flaviviral RNA replication. Dengue and Zika: Advance Experimental Medical Biology, 1062:147-63
Tsheten, T, Clements, A.C., Gray, D.J., Adhikary, R.K., Furuya-Kanamori, L. and Wangdi, K. 2021. Clinical predictors of severe dengue: a systematic review and meta-analysis. Infectious Diseases of Poverty, 10:123.
Uno, N. and Ross, T.M. 2018. Dengue virus and the host innate immune response. Emerging Microbiology Infections, 7(1):1-11.
Vijitha, V.S., Dave, T.V., Murthy, S.I., Ali, M.J., Dave, V.P., Pappuru, R.R. and Narayanan, R. 2021. Severe ocular and adnexal complications in dengue hemorrhagic fever: A report of 29 eyes. Indian Journal of Ophthalmology, 69: 617-622.
Wendling, J.M. and Sabatier, J.M. 2021. Kopferschmitt. La nigelle et le miel: un traitement efficace anti-COVID-19? Dans Hegel, 1:51-56.
Wilken, L. and Rimmelzwaan, G.F. 2020. Adaptive immunity to Dengue virus: Slippery slope or solid ground for rational vaccine design? Pathogens, 9:470.
World Health Organization. Global strategy for dengue prevention and control 2012-2020. https://apps.who.int/iris/bitstream/handle/10665/75303/9789241504034_eng.pdf.
World Health Organization. 2021. Comprehensive guideline for prevention and control of dengue and dengue hemorrhagic fever. Revised and expanded edition. World health Organization, Regional Office for South‒East Asia. 2011.
World Health Organization. 2021. Dengue and severe dengue. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue
Xiao, J., Ke, Z.P., Shi, Y., Zeng, Q. and Cao, Z. 2018. The cardioprotective effect of thymoquinone on ischemia reperfusion injury in isolated rat heart via regulation of apoptosis and autophagy. Journal of Cellular Biochemistry, 119:7212-7217.
Youssoufi, M.H., Sahu, P.K., Sahu, P.K., Agarwal, D.D. Mushtaq, A., Messali, M., Lahsasni, S. and Hadda, T.B. 2015. POM analyses of the antimicrobial activity of 4H-pyrimido[2,1-b]benzothiazole, pyrazole and benzylidene derivatives of curcumin. Medicinal Chemistry Research, 24:2381–2392.