Login Register Cart 0
Generic placeholder image

Current Nutrition & Food Science

Editor-in-Chief

ISSN (Print): 1573-4013
ISSN (Online): 2212-3881

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Role of Pineapple and its Bioactive Compound Bromelain in COVID 19

Author(s): Virender Kumar, Vandana Garg* and Harish Dureja

Volume 20, Issue 3, 2024

Published on: 09 June, 2023

Page: [305 - 316] Pages: 12

DOI: 10.2174/1573401319666230418104554

Price: $65

conference banner
Abstract

Background: Ananas comosus (L.) Merr., which is commonly known as pineapple, is a well-studied plant for its medicinal properties. In terms of commercial importance, it ranks third among tropical fruits. It has been used for its antidiabetic, antimalarial, anticancer, abortifacient, antioxidant, and antidiarrhoeal activities. The review aimed to study the effects of pineapples and their bioactive compounds on the SARS-CoV-2 virus.

Methods: Research methods comprise significant studies on the treatment of COVID-19 utilizing pineapple and its bioactive compounds. To carry out the e-literature review, articles were downloaded from online search engines, including Elsevier, PubMed, and Google Scholar, using pineapple, bioactive compounds, bromelain, clinical trial, and COVID-19.

Results: The literature showed that pineapple and its bioactive compounds showed antiviral effects in COVID-19 patients by inhibiting the proinflammatory cytokines and affecting various signaling molecules, including NF-κB, proinflammatory cytokines, and cyclooxygenase-2. They modulate apoptotic protein levels and also cause a reduction of ACE-2 and TMPRSS2 expression.

Conclusion: For the development of phytomedicine that adheres to all safety regulations, pineapple, and its bioactive compounds can serve as lead molecules for clinical studies in SARS-CoV-2 infection treatment and therapy.

Keywords: Pineapple, bioactive compounds, clinical trials, COVID-19, bromelain SARS-CoV-2, proinflammatory cytokines.

« Previous Next »
Graphical Abstract

[1]
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020; 395(10229): 1054-62.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[2]
Sadhukhan P, Ugurlu MT, Hoque MO. Effect of COVID-19 on lungs: Focusing on prospective malignant phenotypes. Cancers 2020; 12(12): 3822.
[http://dx.doi.org/10.3390/cancers12123822] [PMID: 33352869]
[3]
WHO Coronavirus (COVID-19) Dashboard | WHO coronavirus (COVID-19) dashboard with vaccination data. Available from: https://covid19.who.int/
[4]
Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents 2020; 55(3): 105924.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105924] [PMID: 32081636]
[5]
Schoeman D, Fielding BC. Coronavirus envelope protein: Current knowledge. Virol J 2019; 16(1): 69.
[http://dx.doi.org/10.1186/s12985-019-1182-0] [PMID: 31133031]
[6]
Song W, Gui M, Wang X, Xiang Y. Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog 2018; 14(8): e1007236.
[http://dx.doi.org/10.1371/journal.ppat.1007236]
[7]
Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol 2021; 19(3): 141-54.
[http://dx.doi.org/10.1038/s41579-020-00459-7] [PMID: 33024307]
[8]
Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 2021; 23(1): 3-20.
[9]
Leung NHL. Transmissibility and transmission of respiratory viruses. Nat Rev Microbiol 2021; 19(8): 528-45.
[http://dx.doi.org/10.1038/s41579-021-00535-6] [PMID: 33753932]
[10]
Jayaweera M, Perera H, Gunawardana B, Manatunge J. Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy. Environ Res 2020; 188: 109819.
[http://dx.doi.org/10.1016/j.envres.2020.109819] [PMID: 32569870]
[11]
Wiktorczyk-Kapischke N, Grudlewska-Buda K, Wałecka-Zacharska E, et al. SARS-CoV-2 in the environment - Non-droplet spreading routes. Sci Total Environ 2021; 770: 145260.
[http://dx.doi.org/10.1016/j.scitotenv.2021.145260] [PMID: 33513500]
[12]
Lotfi M, Hamblin MR, Rezaei N. COVID-19: Transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta 2020; 508: 254-66.
[http://dx.doi.org/10.1016/j.cca.2020.05.044] [PMID: 32474009]
[13]
Insuan O, Janchai P, Thongchuai B, Chaiwongsa R, Khamchun S, Saoin S. Anti-inflammatory effect of pineapple rhizome bromelain through downregulation of the NF-κB- and MAPKs-signaling pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Curr Issues Mol Biol 2021; 43(1): 93.
[14]
Ajayi AM, Coker AI, Oyebanjo OT, Adebanjo IM, Ademowo OG. Ananas comosus (L) Merrill (pineapple) fruit peel extract demonstrates antimalarial, anti-nociceptive and anti-inflammatory activities in experimental models. J Ethnopharmacol 2022; 282: 114576.
[http://dx.doi.org/10.1016/j.jep.2021.114576] [PMID: 34461191]
[15]
Xie W, Xing D, Sun H, Wang W, Ding Y, Du L. The effects of Ananas comosus L. leaves on diabetic-dyslipidemic rats induced by alloxan and a high-fat/high-cholesterol diet. Am J Chin Med 2005; 33(1): 95-105.
[http://dx.doi.org/10.1142/S0192415X05002692] [PMID: 15844837]
[16]
Baur X, Fruhmann G. Allergic reactions, including asthma, to the pineapple protease bromelain following occupational exposure. Clin Exp Allergy 1979; 9(5): 443-50.
[http://dx.doi.org/10.1111/j.1365-2222.1979.tb02507.x] [PMID: 498486]
[17]
Praveen NC, Rajesh A, Madan M, Chaurasia VR, Hiremath NV, Sharma AM. In vitro evaluation of antibacterial efficacy of pineapple extract (bromelain) on periodontal pathogens. J Int Oral Health 2014; 6(5): 96-8.
[18]
Seenak P, Kumphune S, Malakul W, Chotima R, Nernpermpisooth N. Pineapple consumption reduced cardiac oxidative stress and inflammation in high cholesterol diet-fed rats. Nutr Metab 2021; 18(1): 36.
[http://dx.doi.org/10.1186/s12986-021-00566-z] [PMID: 33827626]
[19]
Brien S, Lewith G, Walker A, Hicks SM, Middleton D. Bromelain as a treatment for osteoarthritis: A review of clinical studies. Evid Based Complementary Altern Med 2004; 1(3): 251.
[http://dx.doi.org/10.1093/ecam/neh035]
[20]
Aiyegbusi AI, Duru FI, Awelimobor D, Noronha CC, Okanlawon AO. The role of aqueous extract of pineapple fruit parts on the healing of acute crush tendon injury. Nig Q J Hosp Med 2010; 20(4): 223-7.
[21]
Errasti M, Caffini N, Pelzer L, Rotelli A. Anti-inflammatory activity of Bromelia hieronymi: Comparison with bromelain. Planta Med 2013; 79((03/04)): 207-13.
[http://dx.doi.org/10.1055/s-0032-1328201] [PMID: 23364884]
[22]
Bhui K, Prasad S, George J, Shukla Y. Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Cancer Lett 2009; 282(2): 167-76.
[http://dx.doi.org/10.1016/j.canlet.2009.03.003] [PMID: 19339108]
[23]
Search of pineapple - List Results - ClinicalTrials.gov. Available from: https://clinicaltrials.gov/ct2/results?cond=pineapple&term=&cntry=&state=&city=&dist Accessed date: 26.04.2023.
[24]
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 2020; 14(3): 241-6.
[http://dx.doi.org/10.1016/j.dsx.2020.03.011] [PMID: 32247211]
[25]
Wu R, Wang L, Kuo HCD, et al. An update on current therapeutic drugs treating COVID-19. Curr Pharmacol Rep 2020; 6(3): 56-70.
[http://dx.doi.org/10.1007/s40495-020-00216-7] [PMID: 32395418]
[26]
Samavati L, Uhal BD. ACE2, much more than just a receptor for SARS-COV-2. Front Cell Infect Microbiol 2020; 10: 317.
[http://dx.doi.org/10.3389/fcimb.2020.00317] [PMID: 32582574]
[27]
Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020; 581(7807): 221-4.
[28]
Zamorano Cuervo N, Grandvaux N. ACE2: Evidence of role as entry receptor for SARS-CoV-2 and implications in comorbidities. eLife 2020; 9: e61390.
[http://dx.doi.org/10.7554/eLife.61390] [PMID: 33164751]
[29]
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181(2): 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[30]
Gheblawi M, Wang K, Viveiros A, et al. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system. Circ Res 2020; 126(10): 1456-74.
[http://dx.doi.org/10.1161/CIRCRESAHA.120.317015] [PMID: 32264791]
[31]
Xiao T, Lu J, Zhang J, Johnson RI, McKay LGA, Storm N. A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent. Nat Struct Mol Biol 2021; 28(2): 202-9.
[http://dx.doi.org/10.1038/s41594-020-00549-3]
[32]
Towler P, Staker B, Prasad SG, et al. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J Biol Chem 2004; 279(17): 17996-8007.
[http://dx.doi.org/10.1074/jbc.M311191200] [PMID: 14754895]
[33]
Sagar S, Rathinavel AK, Lutz WE, et al. Bromelain inhibits SARS-CoV-2 infection via targeting ACE-2, TMPRSS2, and spike protein. Clin Transl Med 2021; 11(2): e281.
[http://dx.doi.org/10.1002/ctm2.281] [PMID: 33635001]
[34]
Duan L, Zheng Q, Zhang H, Niu Y, Lou Y, Wang H. The SARS-CoV-2 spike glycoprotein biosynthesis, structure, function, and antigenicity: Implications for the design of spike-based vaccine immunogens. Front Immunol 2020; 11: 576622.
[http://dx.doi.org/10.3389/fimmu.2020.576622] [PMID: 33117378]
[35]
Casalino L, Gaieb Z, Goldsmith JA, et al. Beyond shielding: The roles of glycans in the SARS-CoV-2 spike protein. ACS Cent Sci 2020; 6(10): 1722-34.
[http://dx.doi.org/10.1021/acscentsci.0c01056] [PMID: 33140034]
[36]
Starr TN, Greaney AJ, Hilton SK, et al. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 2020; 182(5): 1295-1310.e20.
[http://dx.doi.org/10.1016/j.cell.2020.08.012] [PMID: 32841599]
[37]
Schlegel A, Schaller J, Jentsch P, Kempf C. Semliki forest virus core protein fragmentation: Its possible role in nucleocapsid disassembly. Biosci Rep 1993; 13(6): 333-47.
[http://dx.doi.org/10.1007/BF01150478] [PMID: 8204803]
[38]
Tallei TE, Fatimawali Adam AA, et al. Fruit bromelain-derived peptide potentially restrains the attachment of SARS-CoV-2 variants to hACE2: A pharmacoinformatics approach. Molecules 2022; 27(1): 260.
[http://dx.doi.org/10.3390/molecules27010260] [PMID: 35011492]
[39]
Tallei TE, Fatimawali Yelnetty A, et al. An analysis based on molecular docking and molecular dynamics simulation study of bromelain as Anti-SARS-CoV-2 variants. Front Pharmacol 2021; 12: 717757.
[http://dx.doi.org/10.3389/fphar.2021.717757] [PMID: 34489706]
[40]
Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19). JAMA 2020; 324(8): 782-93.
[http://dx.doi.org/10.1001/jama.2020.12839] [PMID: 32648899]
[41]
Meini S, Zanichelli A, Sbrojavacca R, et al. Understanding the pathophysiology of COVID-19: Could the contact system be the key? Front Immunol 2020; 11: 2014.
[http://dx.doi.org/10.3389/fimmu.2020.02014] [PMID: 32849666]
[42]
Heaton NS, Randall G. Multifaceted roles for lipids in viral infection. Trends Microbiol 2011; 19(7): 368-75.
[http://dx.doi.org/10.1016/j.tim.2011.03.007] [PMID: 21530270]
[43]
Ayres JS. A metabolic handbook for the COVID-19 pandemic. Nat Metab 2020; 2(7): 572-85.
[http://dx.doi.org/10.1038/s42255-020-0237-2] [PMID: 32694793]
[44]
Thai M, Graham NA, Braas D, et al. Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication. Cell Metab 2014; 19(4): 694-701.
[http://dx.doi.org/10.1016/j.cmet.2014.03.009] [PMID: 24703700]
[45]
Moreno-Altamirano MMB, Kolstoe SE, Sánchez-García FJ. Virus control of cell metabolism for replication and evasion of host immune responses. Front Cell Infect Microbiol 2019; 9: 95.
[http://dx.doi.org/10.3389/fcimb.2019.00095] [PMID: 31058096]
[46]
Thaker SK, Ch’ng J, Christofk HR. Viral hijacking of cellular metabolism. BMC Biol 2019; 17(1): 59.
[http://dx.doi.org/10.1186/s12915-019-0678-9] [PMID: 31319842]
[47]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[48]
Lucas C, Wong P, Klein J, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020; 584(7821): 463-9.
[http://dx.doi.org/10.1038/s41586-020-2588-y] [PMID: 32717743]
[49]
Merino-Ramos T, Vázquez-Calvo Á, Casas J, Sobrino F, Saiz JC, Martín-Acebes MA. Modification of the host cell lipid metabolism induced by hypolipidemic drugs targeting the acetyl Coenzyme A carboxylase impairs west nile virus replication. Antimicrob Agents Chemother 2016; 60(1): 307-15.
[http://dx.doi.org/10.1128/AAC.01578-15] [PMID: 26503654]
[50]
Codo AC, Davanzo GG, Monteiro LB, et al. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis-dependent axis. Cell Metab 2020; 32(3): 437-446.e5.
[http://dx.doi.org/10.1016/j.cmet.2020.07.007] [PMID: 32697943]
[51]
Maurer HR. Bromelain: Biochemistry, pharmacology and medical use. Cell Mol Life Sci 2001; 58(9): 1234-45.
[http://dx.doi.org/10.1007/PL00000936] [PMID: 11577981]
[52]
Rowan AD, Buttle DJ. Pineapple cysteine endopeptidases. Methods Enzymol 1994; 244(C): 555-68.
[http://dx.doi.org/10.1016/0076-6879(94)44040-9] [PMID: 7845232]
[53]
Moss JN, Frazier CV, Martin GJ. Bromelains. the pharmacology of the enzymes. Arch Int Pharmacodyn Ther 1963; 145: 166-89.
[54]
Bromelain. Monograph - PubMed [Internet]. Available from: https://pubmed.ncbi.nlm.nih.gov/21194252/ Accessed: 26-04-2023
[55]
Chen L, Deng H, Cui H, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 2018; 9(6): 7204-18.
[http://dx.doi.org/10.18632/oncotarget.23208] [PMID: 29467962]
[56]
Rosales C. Neutrophil: A cell with many roles in inflammation or several cell types? Front Physiol 2018; 9: 113.
[http://dx.doi.org/10.3389/fphys.2018.00113] [PMID: 29515456]
[57]
Merad M, Martin JC. Author Correction: Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages. Nat Rev Immunol 2020; 20(7): 448.
[http://dx.doi.org/10.1038/s41577-020-0331-4]
[58]
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J Infect 2020; 80(6): 607-13.
[http://dx.doi.org/10.1016/j.jinf.2020.03.037] [PMID: 32283152]
[59]
Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev 2020; 54: 62-75.
[http://dx.doi.org/10.1016/j.cytogfr.2020.06.001] [PMID: 32513566]
[60]
Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What we know so far. Front Immunol 2020; 11: 1446.
[http://dx.doi.org/10.3389/fimmu.2020.01446] [PMID: 32612617]
[61]
Hong JH, Kim MR, Lee BN, et al. Anti-inflammatory and mineralization effects of bromelain on lipopolysaccharide-induced inflammation of human dental pulp cells. Medicina 2021; 57(6): 591.
[http://dx.doi.org/10.3390/medicina57060591] [PMID: 34201357]
[62]
Solt LA, May MJ. The IκB kinase complex: Master regulator of NF-κB signaling. Immunol Res 2008; 42(1-3): 3-18.
[http://dx.doi.org/10.1007/s12026-008-8025-1] [PMID: 18626576]
[63]
Bhui K, Tyagi S, Srivastava AK, et al. Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G2/M arrest to apoptosis. Mol Carcinog 2012; 51(3): 231-43.
[http://dx.doi.org/10.1002/mc.20769] [PMID: 21432909]
[64]
Ribes A, Vardon-Bounes F, Mémier V, et al. Thromboembolic events and COVID-19. Adv Biol Regul 2020; 77: 100735.
[http://dx.doi.org/10.1016/j.jbior.2020.100735] [PMID: 32773098]
[65]
Zhang S, Liu Y, Wang X, et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J Hematol Oncol 2020; 13(1): 120.
[http://dx.doi.org/10.1186/s13045-020-00954-7] [PMID: 32887634]
[66]
Iba T, Connors JM, Levy JH. The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res 2020; 69(12): 1181-9.
[http://dx.doi.org/10.1007/s00011-020-01401-6] [PMID: 32918567]
[67]
Fard MB, Fard SB, Ramazi S, Atashi A, Eslamifar Z. Thrombosis in COVID-19 infection: Role of platelet activation-mediated immunity. Thromb J 2021; 19(1): 1-11.
[68]
Rathnavelu V, Alitheen NB, Sohila S, Kanagesan S, Ramesh R. Potential role of bromelain in clinical and therapeutic applications. Biomed Rep 2016; 5(3): 283-8.
[http://dx.doi.org/10.3892/br.2016.720] [PMID: 27602208]
[69]
Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 2020; 26(10): 1636-43.
[70]
Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine Storm in COVID-19: The current evidence and treatment strategies. Front Immunol 2020; 11: 1708.
[http://dx.doi.org/10.3389/fimmu.2020.01708] [PMID: 32754163]
[71]
Wang J, Jiang M, Chen X, Montaner LJ. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol 2020; 108(1): 17-41.
[http://dx.doi.org/10.1002/JLB.3COVR0520-272R] [PMID: 32534467]
[72]
Pavan R, Jain S. Shraddha, Kumar A. Properties and therapeutic application of bromelain: A review. Biotechnol Res Int 2012; 2012: 1-6.
[http://dx.doi.org/10.1155/2012/976203]
[73]
Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol 1988; 22(2): 191-203.
[http://dx.doi.org/10.1016/0378-8741(88)90127-4] [PMID: 3287010]
[74]
Jose RJ, Manuel A. COVID-19 cytokine storm: The interplay between inflammation and coagulation. Lancet Respir Med 2020; 8(6): e46-7.
[http://dx.doi.org/10.1016/S2213-2600(20)30216-2] [PMID: 32353251]
[75]
Catalan MP, Aquino FC, Limjuco RP. Anticoagulant activity of pineapple (Ananas comosus) extract on human blood samples. IAMURE Int J Sci Clin Laboratory 2014; 6(1): 10-7718.
[76]
Kaur H, Corscadden K, Lott C, Elbatarny HS, Othman M. Bromelain has paradoxical effects on blood coagulability. Blood Coagul Fibrinolysis 2016; 27(7): 745-52.
[http://dx.doi.org/10.1097/MBC.0000000000000244] [PMID: 25517253]
[77]
Mason RJ. Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J 2020; 55(4): 2000607.
[http://dx.doi.org/10.1183/13993003.00607-2020] [PMID: 32269085]
[78]
Visualizing what COVID-19 does to your body - visual capitalist. Available from : https://www.visualcapitalist.com/visualizing-what-covid-19-does-to-your-body/
[79]
Esam Z, Taloki ZN, Taloki ZN. Bromelain and its potential therapeutic effects in COVID-19-induced respiratory complications. J Med Res 2020; 6(6): 313-4.
[http://dx.doi.org/10.31254/jmr.2020.6614]
[80]
South AM, Diz DI, Chappell MC. COVID-19, ACE2, and the cardiovascular consequences. Am J Physiol Heart Circ Physiol 2020; 318(5): H1084-90.
[http://dx.doi.org/10.1152/ajpheart.00217.2020] [PMID: 32228252]
[81]
Wang J, Zhao S, Liu M, Zhao Z, Xu Y, Wang P. ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism.2020 Feb 7. Available from : https://www.medrxiv.org/content/10.1101/2020.02.05.20020545v1
[http://dx.doi.org/10.1101/2020.02.05.20020545]
[82]
Chan JFW, Kok KH, Zhu Z, Chu H, To KKW, Yuan S. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect 2020; 9(1): 221-36.
[http://dx.doi.org/10.1080/22221751.2020.1719902]
[83]
Sagar S, Rathinavel AK, Lutz WE, Struble LR, Khurana S, Schnaubelt AT. Bromelain Inhibits SARS-CoV-2 Infection in VeroE6 Cells 2020 Sep 16 Available from : http://www.ncbi.nlm.nih.gov/pubmed/32995771
[http://dx.doi.org/10.1101/2020.09.16.297366]
[84]
Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, evaluation, and treatment of coronavirus (COVID-19).In:StatPearls. Treasure Island, FL: StatPearls Publishing 2022.
[85]
Kritis P, Karampela I, Kokoris S, Dalamaga M. The combination of bromelain and curcumin as an immune-boosting nutraceutical in the prevention of severe COVID-19. Metabolism Open 2020; 8: 100066.
[http://dx.doi.org/10.1016/j.metop.2020.100066] [PMID: 33205039]
[86]
ClinicalTrials.gov. The study of quadruple therapy zinc, quercetin, bromelain and vitamin C on the clinical outcomes of patients infected with COVID-19. Identifier: NCT04468139, Available from : https://clinicaltrials.gov/ct2/show/NCT04468139
[87]
Akhter J, Quéromès G, Pillai K, et al. The combination of bromelain and acetylcysteine (BromAc) synergistically inactivates SARS-CoV-2. Viruses 2021; 13(3): 425.
[http://dx.doi.org/10.3390/v13030425] [PMID: 33800932]
[88]
ClinicalTrials.gov. New antiviral drugs for treatment of COVID-19. ClinicalTrials.gov Identifier: NCT04392427, Available from : https://clinicaltrials.gov/ct2/show/NCT04392427
[89]
Peter AE, Sandeep BV, Rao BG, Kalpana VL. Calming the Storm: Natural immunosuppressants as adjuvants to target the cytokine storm in COVID-19. Front Pharmacol 2021; 11: 583777.
[http://dx.doi.org/10.3389/fphar.2020.583777] [PMID: 33708109]
[90]
Ang L, Song E, Lee HW, Lee MS. Herbal Medicine for the Treatment of Coronavirus Disease 2019 (COVID-19): A systematic review and meta-analysis of randomized controlled trials. J Clin Med 2020; 9(5): 1583.
[http://dx.doi.org/10.3390/jcm9051583] [PMID: 32456123]
[91]
Seligman B. Bromelain: An anti-inflammatory agent. Angiology 1962; 13(11): 508-10.
[http://dx.doi.org/10.1177/000331976201301103] [PMID: 13992714]

Rights & Permissions Print Cite
Article Metrics
11
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy