Unlocking the Potential of Carica papaya L.: A Comprehensive Review on Its Antiviral Activity and Therapeutic Role in Dengue Management

Ahmad, N., Fazal, H., Ayaz, M., Abbasi, B. H., Mohammad, I., & Fazal, L. (2011). Dengue fever treatment with Carica papaya leaves extracts. Asian Pacific Journal of Tropical Biomedicine, 1(4), 330–333. https://doi.org/10.1016/S2221-1691(11)60055-5

Amri, E., & Mamboya, F. (2012). Papain, a plant enzyme of biological importance: A review. American Journal of Biochemistry and Biotechnology, 8(2), 99–104. https://doi.org/10.3844/ajbbsp.2012.99.104

Anjum, V., Arora, P., Ansari, S. H., Najmi, A. K., & Ahmad, S. (2017). Antithrombocytopenic and immunomodulatory potential of metabolically characterized aqueous extract of Carica papaya leaves. Pharmaceutical Biology, 55(1), 2043–2056. https://doi.org/10.1080/13880209.2017.1346690

Aruoma, O. I., Colognato, R., Fontana, I., Gartlon, J., Migliore, L., Koike, K., Coecke, S., Goldfinger, V., Bolaños-Jiménez, F., Cosialls, A. M., & Guimarães, A. M. (2006). Molecular effects of fermented papaya preparation on oxidative damage, MAP kinase activation and modulation of the benzo[a]pyrene mediated genotoxicity. BioFactors, 26(2), 147–159. https://doi.org/10.1002/biof.5520260205

Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., & Supuran, C. T. (2021). Natural products in drug discovery: Advances and opportunities. Nature Reviews Drug Discovery, 20(3), 200–216. https://doi.org/10.1038/s41573-020-00114-z

Barros, T. A. da C., & de-Oliveira-Pinto, L. M. (2018). A view of platelets in dengue. In P. Valent (Ed.), Thrombocytopenia (pp. 1–22). IntechOpen. https://doi.org/10.5772/intechopen.73084

Bhatt, S., Gething, P. W., Brady, O. J., Messina, J. P., Farlow, A. W., Moyes, C. L., Drake, J. M., Brownstein, J. S., Hoen, A. G., Sankoh, O., Myers, M. F., George, D. B., Jaenisch, T., Wint, G. R. W., Simmons, C. P., Scott, T. W., Farrar, J. J., & Hay, S. I. (2013). The global distribution and burden of dengue. Nature, 496(7446), 504–507. https://doi.org/10.1038/nature12060

Bhowmik, D. (2013). Traditional and medicinal uses of Carica papaya. Journal of Medicinal Plants Studies, 1(1), 7–15.

Chambers, T. J., Hahn, C. S., Galler, R., & Rice, C. M. (1990). Flavivirus genome organization, expression, and replication. Annual Review of Microbiology, 44, 649–688. https://doi.org/10.1146/annurev.mi.44.100190.003245

Charan, J., Saxena, D., Goyal, J., & Yasobant, S. (2016). Efficacy and safety of Carica papaya leaf extract in the dengue: A systematic review and meta-analysis. International Journal of Applied and Basic Medical Research, 6(4), 249–254. https://doi.org/10.4103/2229-516x.192596

Chen, Y., Liu, Y., Sarker, M. M. R., Yan, X., Yang, C., Zhao, L., Li, B., Zhao, M., Zhang, J., Wu, J., & Ren, G. (2018). Structural characterization and antidiabetic potential of a novel heteropolysaccharide from Grifola frondosa via IRS1/PI3K-JNK signaling pathways. Carbohydrate Polymers, 198, 452–461. https://doi.org/10.1016/j.carbpol.2018.06.077

Cheng, S. C., Wu, Y. H., Huang, W. C., Pang, J. H. S., Huang, T. H., & Cheng, C. Y. (2019). Anti-inflammatory property of quercetin through downregulation of ICAM-1 and MMP-9 in TNF-α-activated retinal pigment epithelial cells. Cytokine, 116, 48–60. https://doi.org/10.1016/j.cyto.2019.01.001

Chinaka, U. E. N., & Nwosu, O. (2013). Anti-fertility effects of Carica papaya Linn.: Methanol leaf extracts in male Wistar rats. Journal of Pharmacology and Toxicology, 8(1), 35–41.

Chinnappan, S., Shettikothanuru Ramachandrappa, V., Tamilarasu, K., Krishnan, U. M., Balakrishna Pillai, A. K., & Rajendiran, S. (2016). Inhibition of platelet aggregation by the leaf extract of Carica papaya during dengue infection: An in vitro study. Viral Immunology, 29(3), 164–168. https://doi.org/10.1089/vim.2015.0083

Das, S. K., Sengupta, P., Mustapha, M. S., & Sarker, M. M. R. (2017). An experimental evaluation of adaptogenic potential of standardized Epipremnum aureum leaf extract. Journal of Pharmacy and Bioallied Sciences, 9(2), 88–93. https://doi.org/10.4103/0975-7406.183227

Dawkins, G., Hewitt, H., Wint, Y., Obiefuna, P. C., & Wint, B. (2003). Antibacterial effects of Carica papaya fruit on common wound organisms. West Indian Medical Journal, 52(4), 290–292. https://pubmed.ncbi.nlm.nih.gov/15040064/

Deen, E. (2009). Dengue: Clinical and public health ramifications. Australian Family Physician, 38(11), 876–879.

De Souza, L. M., Ferreira, K. S., Chaves, J. B. P., & Teixeira, S. L. (2008). L-ascorbic acid, β-carotene and lycopene content in papaya fruits (Carica papaya) with or without physiological skin freckles. Scientia Agricola, 65(3), 246–250. https://doi.org/10.1590/S0103-90162008000300004

Dhanamani, M., Devi, S. L., & Kannan, S. (2011). Ethnomedicinal plants for cancer therapy: A review. Hygeia Journal for Drugs and Medicines, 3(1), 1–10.

Doughari, J. H., & Manzara, A. M. (2007). Studies on the antibacterial activity of root extracts of Carica papaya L. African Journal of Microbiology Research.

Duke, J. A. (2022). Dr. Duke’s phytochemical and ethnobotanical databases. United States Department of Agriculture. https://phytochem.nal.usda.gov/phytochem/search

Edeoga, H. O., & Eriata, D. O. (2001). Alkaloid, tannin and saponin contents of some Nigerian medicinal plants. Journal of Medicinal and Aromatic Plant Sciences, 23, 344–349.

Ekong, M. B., Akpan, M. U., Ekanem, T. B., & Akpaso, M. I. (2011). Morphometric malformations in fetal rats following treatment with aqueous leaf extract of Carica papaya. International Journal of Applied and Basic Medical Research, 2(1), 27–31.

Erasto, P., Grierson, D. S., & Afolayan, A. J. (2007). Antioxidant constituents in Vernonia amygdalina leaves. Pharmaceutical Biology, 45(3), 195–199. https://doi.org/10.1080/13880200701213070

Gadhwal, A. K., Ankit, B. S., Chahar, C., Tantia, P., Sirohi, P., & Agrawal, R. P. (2016). Effect of Carica papaya leaf extract capsule on platelet count in patients of dengue fever with thrombocytopenia. Journal of the Association of Physicians of India, 64(6), 22–26. https://europepmc.org/article/MED/27739263

Gardi, C., Bauerova, K., Stringa, B., Kuncirova, V., Slovak, L., Ponist, S., Drafi, F., Bezakova, L., Tedesco, I., Acquaviva, A., & Bilotto, S. (2015). Quercetin reduced inflammation and increased antioxidant defense in rat adjuvant arthritis. Archives of Biochemistry and Biophysics, 583, 150–157. https://doi.org/10.1016/j.abb.2015.08.008

Gaunt, M. W., Sall, A. A., De Lamballerie, X., Falconar, A. K. I., Dzhivanian, T. I., & Gould, E. A. (2001). Phylogenetic relationships of flaviviruses correlate with their epidemiology, disease association and biogeography. Journal of General Virology, 82(8), 1867–1876.

Gayosso-García Sancho, L. E., Yahia, E. M., & González-Aguilar, G. A. (2011). Identification and quantification of phenols, carotenoids, and vitamin C from papaya (Carica papaya L., cv. Maradol) fruit determined by HPLC-DAD-MS/MS-ESI. Food Research International, 44(5), 1284–1291. https://doi.org/10.1016/j.foodres.2010.12.001

Gebhardt, S. E., Thomas, R. G., & United States Agricultural Research Service. (2002). Nutritive value of foods. U.S. Department of Agriculture, Agricultural Research Service.

Giordani, R., Gachon, C., Moulin-Traffort, J., & Régli, P. (1997). A synergistic effect of Carica papaya latex sap and fluconazole on Candida albicans growth. Mycoses, 40(11–12), 429–437.

Gomes, M. T. R., Mello, V. J., Rodrigues, K. C., Bemquerer, M. P., Presente, A., Oliveira, A. E. A., Guimarães, V. M., & Magalhães, A. (2005). Isolation of two plant proteinases in latex from Carica candamarcensis acting as mitogens for mammalian cells. Planta Medica, 71(3), 244–248. https://doi.org/10.1055/s-2005-837824

Goto, T., Sarker, R., Zhong, M., Tanaka, S., & Gohda, E. (2010). Enhancement of immunoglobulin M production in B cells by the extract of red bell pepper. Phytotherapy Research, 56(11), 1629–1637.

Grumezescu, A. M., & Holban, A. M. (Eds.). (2019). Fermented beverages: The science of beverages (Vol. 5). Woodhead Publishing.

Gupta, N., Srivastava, S., Jain, A., & Chaturvedi, U. C. (2012). Dengue in India. Indian Journal of Medical Research, 136(3), 373–390.

Gupta, R., Sharma, A. K., Dobhal, M. P., Sharma, M. C., & Gupta, R. S. (2011). Antidiabetic and antioxidant potential of β-sitosterol in streptozotocin-induced experimental hyperglycemia. Journal of Diabetes, 3(1), 29–37. https://doi.org/10.1111/j.1753-0407.2010.00107.x

Hadinegoro, S. R., Arredondo-García, J. L., Capeding, M. R., Deseda, C., Chotpitayasunondh, T., Dietze, R., Ismail, H. I. H. M., Reynales, H., Limkittikul, K., Rivera-Medina, D. M., Tran, H. N., Bouckenooghe, A., Chansinharaj, D., Gardien, E., Laot, T., Sidiqui, S., Thielemans, L., Wartel, A., Beurier, M. D., … Noriega, F. (2015). Efficacy and long-term safety of a dengue vaccine in regions of endemic disease. New England Journal of Medicine, 373(13), 1195–1206. https://doi.org/10.1056/nejmoa1506223

Haleagrahara, N., Hodgson, K., Miranda-Hernandez, S., Hughes, S., Kulur, A. B., & Ketheesan, N. (2018). Flavonoid quercetin–methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis. Inflammopharmacology, 26(5), 1219–1232. https://doi.org/10.1007/s10787-018-0464-2

Halstead, S. B. (1974). Etiologies of the experimental dengues of Siler and Simmons. American Journal of Tropical Medicine and Hygiene, 23(5), 974–982. https://doi.org/10.4269/ajtmh.1974.23.974

Henchal, E. A., & Putnak, J. R. (1990). The dengue viruses. Clinical Microbiology Reviews, 3(4), 376–396.

Hettige, S. H. (2008). Salutary effects of Carica papaya leaf extract in dengue fever patients: A pilot study. Sri Lankan Family Physician, 29, 17–19.

Huet, J., Looze, Y., Bartik, K., Raussens, V., Wintjens, R., & Boussard, P. (2006). Structural characterization of the papaya cysteine proteinases at low pH. Biochemical and Biophysical Research Communications, 341(2), 620–626. https://doi.org/10.1016/j.bbrc.2005.12.210

Ibrahim, N. I., Muhammad Ismail Tadj, N. B., Rahman Sarker, M. M., & Naina Mohamed, I. (2020). The potential mechanisms of the neuroprotective actions of oil palm phenolics: Implications for neurodegenerative diseases. Molecules, 25(21), Article 5159. https://doi.org/10.3390/molecules25215159

Ikram, E. H. K., Stanley, R., Netzel, M., & Fanning, K. (2015). Phytochemicals of papaya and its traditional health and culinary uses: A review. Journal of Food Composition and Analysis, 41, 201–211. https://doi.org/10.1016/j.jfca.2015.02.010

Iwamoto, T., Okamoto, H., Toyama, Y., & Momohara, S. (2008). Molecular aspects of rheumatoid arthritis: Chemokines in the joints of patients. FEBS Journal, 275(18), 4448–4455. https://doi.org/10.1111/j.1742-4658.2008.06580.x

Jayasinghe, C. D., Gunasekera, D. S., De Silva, N., Jayawardena, K. K. M., & Udagama, P. V. (2017). Mature leaf concentrate of Sri Lankan wild type Carica papaya Linn. modulates nonfunctional and functional immune responses of rats. BMC Complementary and Alternative Medicine, 17(1), Article 370. https://doi.org/10.1186/s12906-017-1742-z

Johnson, A. J., & Roehrig, J. T. (1999). New mouse model for dengue virus vaccine testing. Journal of Virology, 73(1), 783–786.

Kanatiwela de Silva, C., Daya Ratnasooriya, W., Fernando, C. A., & Vidya Udagama, P. (2011). Thrombocytosis and anti-inflammatory properties, and toxicological evaluation of Carica papaya mature leaf concentrate in a murine model. Journal of Pharmacological Reports, 1(3), 1–10.

Kasture, P., Nagabhushan, K. H., Bhatt, N. D., Bhatt, J. K., Lad, R. S., Jain, A. K., & Shah, P. (2016). A multi-centric, double-blind, placebo-controlled, randomized, prospective study to evaluate the efficacy and safety of Carica papaya leaf extract, as empirical therapy for thrombocytopenia associated with dengue fever. Asian Journal of Pharmaceutical and Clinical Research, 9(2), 154–158.

Kumar, S., & Gupta, V. (2012). Papaya leaves for speedy rise of platelet count in dengue. International Journal of Pharmaceutical Sciences and Research, 3(8), 2788–2790.

Kuno, G., Chang, G. J. J., Tsuchiya, K. R., Karabatsos, N., & Cropp, C. B. (1998). Phylogeny of the genus Flavivirus. Journal of Virology, 72(1), 73–83. https://doi.org/10.1128/jvi.72.1.73-83.1998

Lee, T. H., Lee, L. K., Lye, D. C., & Leo, Y. S. (2017). Current management of severe dengue infection. Expert Review of Anti-Infective Therapy, 15(1), 67–78. https://doi.org/10.1080/14787210.2017.1248405

Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M. T., Wang, S., Liu, H., & Yin, Y. (2016). Quercetin, inflammation and immunity. Nutrients, 8(3), Article 167. https://doi.org/10.3390/nu8030167

Lim, X. Y., Chan, J. S. W., Japri, N., Lee, J. C., & Tan, T. Y. C. (2021). Carica papaya L. leaf: A systematic scoping review on biological safety and herb-drug interactions. Evidence-Based Complementary and Alternative Medicine, 2021, Article 5511221. https://doi.org/10.1155/2021/5511221

Lydia, E., Riyazudin, M., John, S., & Thiyagarajan, S. (2016). Investigation on the phytochemicals present in the fruit peel of Carica papaya and evaluation of its antioxidant properties. International Journal of Health and Allied Sciences, 5(4), 247. https://doi.org/10.4103/2278-344x.194127

Marfo, E. K., Oke, O. L., & Afolabi, O. A. (1986). Some studies on the proteins of Carica papaya seeds. Food Chemistry, 22(4), 267–277. https://doi.org/10.1016/0308-8146(86)90085-3

McRedmond, J. P., Park, S. D., Reilly, D. F., Coppinger, J. A., Maguire, P. B., Shields, D. C., & Fitzgerald, D. J. (2004). Integration of proteomics and genomics in platelets: A profile of platelet proteins and platelet-specific genes. Molecular & Cellular Proteomics, 3(2), 133–144. https://doi.org/10.1074/mcp.M300063-MCP200

Mehdipour, S., Yasa, N., Dehghan, G., Khorasani, R., Mohammadirad, A., Rahimi, R., & Abdollahi, M. (2006). Antioxidant potentials of Iranian Carica papaya juice in vitro and in vivo are comparable to α-tocopherol. Phytotherapy Research, 20(7), 591–594. https://doi.org/10.1002/ptr.1932

Miean, K. H., & Mohamed, S. (2001). Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. Journal of Agricultural and Food Chemistry, 49(6), 3106–3112. https://doi.org/10.1021/jf000892m

Milligan, G. N., Sarathy, V. V., White, M. M., Greenberg, M. B., Campbell, G. A., Pfeifer, B. A., Bhatt, A., & Barrett, A. D. T. (2017). A lethal model of disseminated dengue virus type 1 infection in AG129 mice. Journal of General Virology, 98(10), 2507–2519. https://doi.org/10.1099/jgv.0.000923

Mlcek, J., Jurikova, T., Skrovankova, S., & Sochor, J. (2016). Quercetin and its anti-allergic immune response. Molecules, 21(5), Article 623. https://doi.org/10.3390/molecules21050623

Moklesur, M., Sarker, R., Imam, H., Rokonuzzaman, S. M., Shilpi, J. A., Islam, M. A., & Hossain, H. (2014). In vitro assessment of Prasarani Sandhan, a traditional polyherbal Ayurvedic medicine, for immunostimulating activity in splenic cells of BALB/c mice. Asian Pacific Journal of Tropical Biomedicine, 4(Suppl 1), S189–S194.

Moklesur Rahman Sarker, M., Zihad, M., Islam, M., Rokonuzzaman, S. M., & Shilpi, J. A. (2015). Antihyperglycemic, insulin-sensitivity and antihyperlipidemic potential of Ganoderma lucidum, a dietary mushroom, on alloxan- and glucocorticoid-induced diabetic long-Evans rats. Journal of Diabetes & Metabolic Disorders, 5, 12.

Munira, S., Nesa, L., Islam, M. S., Hossen, M. F., Sarker, M. M. R., Hasan, A. H. M. S., & Shilpi, J. A. (2020). Antidiabetic activity of Neolamarckia cadamba (Roxb.) Bosser flower extract in alloxan-induced diabetic rats. Clinical Phytoscience, 6(1), Article 22. https://doi.org/10.1186/s40816-020-00183-y

Mwelasi, P. P. (2015). Analysis of phenolic compounds in Carica papaya, Zingiber officinale, Ipomoea batatas and Myrothamnus flabellifolius using RP-HPLC-UV/VIS-DAD, and in vitro evaluation of antifungal activity on plant pathogenic fungi of economic importance [Master’s thesis, University of Johannesburg].

Nesa, M. L., Karim, S. M. S., Api, K., Mohiuddin, A. K. M., Sarker, M. M. R., Islam, M., Rahmatullah, M., & Shilpi, J. A. (2018). Screening of Baccaurea ramiflora (Lour.) extracts for cytotoxic, analgesic, anti-inflammatory, neuropharmacological and antidiarrheal activities. BMC Complementary and Alternative Medicine, 18(1), Article 214. https://doi.org/10.1186/s12906-018-2100-5

Ojimelukwe, P., Nwofia, E., Ojimelukwe, P., & Eji, C. (2012). Chemical composition of leaves, fruit pulp and seeds in some Carica papaya (L.) morphotypes. International Journal of Plant Physiology and Biochemistry, 2(2), 1–9.

Okoko, T., & Ere, D. (2012). Reduction of hydrogen peroxide-induced erythrocyte damage by Carica papaya leaf extract. Asian Pacific Journal of Tropical Biomedicine, 2(6), 449–453. https://doi.org/10.1016/S2221-1691(12)60074-4

Olanrewaju, O., Akinloye, O. O., & Morayo, O. M. (2010). Evaluation of andrological indices and testicular histology following chronic administration of aqueous extract of Carica papaya leaf in Wistar rat. African Journal of Pharmacy and Pharmacology, 4(5), 252–255.

Pan American Health Organization. (2018, November 21). Dengue—Epidemiological alert. https://www.paho.org/en/documents/21-november-2018-dengue-epidemiological-alert

Pandita, A., Mishra, N., Gupta, G., & Singh, R. (2019). Use of papaya leaf extract in neonatal thrombocytopenia. Clinical Case Reports, 7(3), 497–499. https://doi.org/10.1002/ccr3.2025

Peristiowati, Y., & Puspitasari, Y. (2017). Acute and subchronic toxicity tests of papaya leaf (Carica papaya L.) methanol extract on Wistar strain white mice. Journal of Applied Environmental and Biological Sciences, 7(11), 9–14.

Prakash Kala, C. (2012). Leaf juice of Carica papaya L.: A remedy of dengue fever. Medicinal & Aromatic Plants, 1(6), Article 109. https://doi.org/10.4172/2167-0412.1000109

Rajapakse, S. (2009). Intravenous immunoglobulins in the treatment of dengue illness. Transactions of the Royal Society of Tropical Medicine and Hygiene, 103(9), 867–870. https://doi.org/10.1016/j.trstmh.2008.12.011

Rajapakse, S., Rodrigo, C., Maduranga, S., & Rajapakse, A. C. (2014). Corticosteroids in the treatment of dengue shock syndrome. Infection and Drug Resistance, 7, 137–143. https://doi.org/10.2147/IDR.S55380

Rajapakse, S., Wattegama, M., Weeratunga, P., Sigera, P. C., & Fernando, S. D. (2018). Beyond thrombocytopaenia, haemorrhage and shock: The expanded dengue syndrome. Pathogens and Global Health, 112(8), 404–414. https://doi.org/10.1080/20477724.2018.1552645

Ranasinghe, P., Ranasinghe, P., Kaushalya, W. P., Jayawardena, R., Hettiarachchi, P., & Katulanda, P. (2012). In vitro erythrocyte membrane stabilization properties of Carica papaya L. leaf extracts. Pharmacognosy Research, 4(4), 196–202. https://doi.org/10.4103/0974-8490.102261

Reddy, D. V., Sudarshana, M. R., Fuchs, M., Rao, N. C., & Thottappilly, G. (2009). Genetically engineered virus-resistant plants in developing countries: Current status and future prospects. Advances in Virus Research, 75, 185–220. https://doi.org/10.1016/s0065-3527(09)07506-x

Rico-Hesse, R. (1990). Molecular evolution and distribution of dengue viruses type 1 and 2 in nature. Virology, 174(2), 479–493.

Ridzuan Mohd Abd Razak, M., Azrina Norahmad, N., Hana Md Jelas, N., Shu-Yih, C., Mohd Ridzuan, M. A. R., & Surendra, K. P. (2021). Immunomodulatory activities of Carica papaya L. leaf juice in a non-lethal, symptomatic dengue mouse model. Pathogens, 10(5), Article 535. https://doi.org/10.3390/pathogens10050535

Rivera-Pastrana, D. M., Yahia, E. M., & González-Aguilar, G. A. (2010). Phenolic and carotenoid profiles of papaya fruit (Carica papaya L.) and their contents under low temperature storage. Journal of the Science of Food and Agriculture, 90(14), 2358–2365. https://doi.org/10.1002/jsfa.4092

Rosen, L., Shroyer, D. A., Tesh, R. B., Freier, J. E., & Lien, J. C. (1983). Transovarial transmission of dengue viruses by mosquitoes: Aedes albopictus and Aedes aegypti. American Journal of Tropical Medicine and Hygiene, 32(5), 1108–1119.

Ruiz, P. A., Braune, A., Hölzlwimmer, G., Quintanilla-Fend, L., & Haller, D. (2007). Quercetin inhibits TNF-induced NF-κB transcription factor recruitment to proinflammatory gene promoters in murine intestinal epithelial cells. Journal of Nutrition, 137(5), 1208–1215. https://doi.org/10.1093/jn/137.5.1208

Sadek, K. M. (2012). Antioxidant and immunostimulant effect of Carica papaya Linn. aqueous extract in acrylamide intoxicated rats. Acta Informatica Medica, 20(3), 180–185. https://doi.org/10.5455/aim.2012.20.180-185

Sarathy, V. V., Milligan, G. N., Bourne, N., & Barrett, A. D. T. (2015). Mouse models of dengue virus infection for vaccine testing. Vaccine, 33(50), 7051–7060. https://doi.org/10.1016/j.vaccine.2015.09.112

Sarathy, V. V., White, M., Li, L., Kaiser, J. A., Campbell, G. A., Milligan, G. N., Bourne, N., & Barrett, A. D. T. (2018). Characterization of a murine model of non-lethal, symptomatic dengue virus infection. Scientific Reports, 8(1), Article 4559. https://doi.org/10.1038/s41598-018-22618-w

Sarker, M. M. R. (2012). Induction of humoral immunity through the enhancement of IgM production in murine splenic cells by ethanolic extract of seed of Piper nigrum L. Journal of Scientific Research, 4(3), 751–756. https://doi.org/10.3329/jsr.v4i3.10485

Sarker, M. M. R. (2021). Evaluation of red and green colored bell peppers for the production of polyclonal IgM and IgG antibodies in murine spleen cells. Bangladesh Pharmaceutical Journal, 24(1), 45–53. https://doi.org/10.3329/bpj.v24i1.51635

Sarker, M. M. R., & Gohda, E. (2013). Promotion of anti-keyhole limpet hemocyanin IgM and IgG antibody productions in vitro by red bell pepper extract. Journal of Functional Foods, 5(4), 1918–1926. https://doi.org/10.1016/j.jff.2013.09.013

Sarker, M. M. R., Ming, L. C., Sarker, Z. I., & Choudhuri, M. S. K. (2016). Immunopotentiality of Ayurvedic polyherbal formulations “Saribadi” and “Anantamul Salsa” with augmentation of IgM production and lymphocytes proliferation: A preliminary study. Asian Pacific Journal of Tropical Biomedicine, 6(7), 568–573. https://doi.org/10.1016/j.apjtb.2016.05.004

Sathyapalan, D. T., Padmanabhan, A., Moni, M., Selvaraj, S., Mohan, A., Vellaringatt, P., Thomas, S. K., & Thomas, T. (2020). Efficacy and safety of Carica papaya leaf extract (CPLE) in severe thrombocytopenia (≤30,000/μl) in adult dengue: Results of a pilot study. PLOS ONE, 15(2), Article e0228699. https://doi.org/10.1371/journal.pone.0228699

Schweiggert, R. M., Steingass, C. B., Esquivel, P., & Carle, R. (2012). Chemical and morphological characterization of Costa Rican papaya (Carica papaya L.) hybrids and lines with particular focus on their genuine carotenoid profiles. Journal of Agricultural and Food Chemistry, 60(10), 2577–2585. https://doi.org/10.1021/jf2045069

Science, E., Development Inst., Nigeria, C. J., & Biological Sciences Kashari. (2017). Phytochemical and antibacterial activity of Carica papaya root extract on some selected pathogens. Science Education Development Institute, 10(2), 27–37. https://doi.org/10.5281/zenodo.1129336

Seigler, D. S., Pauli, G. F., Nahrstedt, A., & Leen, R. (2002). Cyanogenic allosides and glucosides from Passiflora edulis and Carica papaya. Phytochemistry, 60(8), 873–882. https://doi.org/10.1016/S0031-9422(02)00170-X

Senthilvel, P., Lavanya, P., Murugan Kumar, K., Swetha, R., Anitha, P., Bag, S., Bhatt, J., Kumar, S., Pandian, R., & Biswal, S. (2013). Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents dengue 2 viral assembly. Bioinformation, 9(18), 889–895.

Shajib, M. S., Rashid, R. B., Ming, L. C., Sarker, M. M. R., Rashid, M. A., Shahriar, M., & Bhuiyan, M. A. (2018). Polymethoxyflavones from Nicotiana plumbaginifolia (Solanaceae) exert antinociceptive and neuropharmacological effects in mice. Frontiers in Pharmacology, 9, Article 85. https://doi.org/10.3389/fphar.2018.00085

Sharma, N., Mishra, K. P., Chanda, S., Bhardwaj, V., Tanwar, H., Bhatt, D., Ram, G., Kumar, B., & Ganju, L. (2019). Evaluation of anti-dengue activity of Carica papaya aqueous leaf extract and its role in platelet augmentation. Archives of Virology, 164(4), 1095–1110. https://doi.org/10.1007/s00705-019-04179-z

Sheikh, B. Y., Sarker, M. M. R., Kamarudin, M. N. A., & Ismail, A. (2017). Prophetic medicine as potential functional food elements in the intervention of cancer: A review. Biomedicine & Pharmacotherapy, 95, 614–648. https://doi.org/10.1016/j.biopha.2017.08.043

Shresta, S., Sharar, K. L., Prigozhin, D. M., Beatty, P. R., & Harris, E. (2006). Murine model for dengue virus-induced lethal disease with increased vascular permeability. Journal of Virology, 80(20), 10208–10217. https://doi.org/10.1128/jvi.00062-06

Siddique, O., Sundus, A., & Faisal, I. (2014). Effects of papaya leaves on thrombocyte counts in dengue: A case report. Journal of the Pakistan Medical Association, 64(3), 364–366.

Srikanth, B., Reddy, L., Biradar, S., Shamanna, M., Mariguddi, D. D., & Krishnakumar, M. (2019). An open-label, randomized prospective study to evaluate the efficacy and safety of Carica papaya leaf extract for thrombocytopenia associated with dengue fever in pediatric subjects. Pediatric Health, Medicine and Therapeutics, 10, 5–11. https://doi.org/10.2147/phmt.s176712

Subenthiran, S., Choon, T. C., Cheong, K. C., Thayan, R., Teck, M. B., Muniandy, P. K., Afzan, A., Abdullah, N. R., & Ismail, Z. (2013). Carica papaya leaves juice significantly accelerates the rate of increase in platelet count among patients with dengue fever and dengue haemorrhagic fever. Evidence-Based Complementary and Alternative Medicine, 2013, Article 616737. https://doi.org/10.1155/2013/616737

Sundarmurthy, D., Jayanthi, C. R., & Lakshmaiah, K. C. (2017). Effect of Carica papaya leaf extract on platelet count in chemotherapy-induced thrombocytopenic patients: A preliminary study. National Journal of Physiology, Pharmacy and Pharmacology, 7(7), 685–692. https://doi.org/10.5455/njppp.2017.7.0202628022017

Taheri Rouhi, S. Z., Sarker, M. M. R., Rahmat, A., Alkahtani, S. A., & Othman, F. (2017). Erratum: The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Dawley rats. BMC Complementary and Alternative Medicine, 17(1), Article 376. https://doi.org/10.1186/s12906-017-1724-1

Takahashi, H., Takahashi, C., Moreland, N. J., Chang, Y.-T., Sawasaki, T., Ryo, A., Vasudevan, S. G., Suzuki, Y., & Yamamoto, N. (2012). Establishment of a robust dengue virus NS3-NS5 binding assay for identification of protein-protein interaction inhibitors. Antiviral Research, 96(3), 305–314. https://doi.org/10.1016/j.antiviral.2012.09.023

United States Department of Agriculture. (2014). USDA national nutrient database for standard reference.

Wall, M. M. (2006). Ascorbic acid, vitamin A, and mineral composition of banana (Musa sp.) and papaya (Carica papaya) cultivars grown in Hawaii. Journal of Food Composition and Analysis, 19(5), 434–445. https://doi.org/10.1016/j.jfca.2006.01.002

World Health Organization. (2009). Dengue: Guidelines for diagnosis, treatment, prevention and control. https://www.who.int/publications/i/item/9789241547871

Yogiraj, V., Goyal, P. K., Chauhan, C. S., Goyal, A., & Vyas, B. (2014). Carica papaya Linn.: An overview. International Journal of Herbal Medicine, 2(5), 1–8.

Yuliani, R., & Syahdeni, F. (2020). Ethanolic extract of papaya leaves (Carica papaya) and its fractions have no potential cytotoxicity on T47D cells. Pharmacon, 17(1), 1–8.

Yunita, F., Hanani, E., & Kristianto, J. (2012). The effect of Carica papaya L. leaves extract capsules on platelets counts and hematocrit level in dengue fever patient. International Journal of Research in Ayurveda and Pharmacy, 2(4), 1235–1238.

Zaleha Halim, S., Afzan, A., Amini Abd Rashid, B., & Jantan, I. (2011). Acute toxicity study of Carica papaya leaf extract in Sprague Dawley rats. Journal of Medicinal Plants Research, 5(18), 4523–4529.

Zheng, W., Wu, H., Wang, T., Zhan, S., & Liu, X. (2021). Quercetin for COVID-19 and dengue co-infection: A potential therapeutic strategy of targeting critical host signal pathways triggered by SARS-CoV-2 and DENV. Briefings in Bioinformatics, 22(6), Article bbab199. https://doi.org/10.1093/bib/bbab199