Therapeutic Potential of Pomegranate in SARS-CoV-2 and Acute Respiratory Distress Syndrome (ARDS)
European Journal of Medicinal Plants,
Page 1-16
DOI:
10.9734/ejmp/2022/v33i121109
Abstract
COVID-19 is a viral disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which has rapidly spread across the world causing a global health crisis. Due to the paucity of therapeutics against SARS-CoV-2, there is an urgent need for the identification of safe and effective treatments for this global pandemic. Thus, existing anti-viral and immunosuppressive drugs, are being evaluated as potential candidates and also an extensive amount of research is being conducted to develop novel therapeutic agents against COVID-19. Since ancient times natural products have been used as a treatment for a variety of diseases and to aid in the synthetic drug development process. The phytochemical constituents of Pomegranate have been extensively investigated in the past decade for their anti-tumor activity. The purpose of this review is to elaborate on how the major phytochemicals of pomegranate such as delphinidin, cyanidin, ellagitannin, and punicalagin could be utilized as pharmacological agents to suppress SARS-CoV-2 cell entry, replication, and immunological sequences that give rise to ARDS, based on current knowledge of interactome between host cells and SARS-CoV-2. The SARS-CoV-2 uses various biological mechanisms to modulate immune reactions, uncontrolled gene expression, and cell invasion to improve their survival inside the human host cells similar to those observed in certain tumors. Existing evidence suggests that certain tumors and SARS-CoV-2 use similar biological pathways for human cell invasion. Therefore, this review utilizes the findings of existing tumor-related research which describe how pomegranate extract interacts with various biological pathways associated with tumor suppression as indirect evidence for its ability to act as a potential therapeutic agent against SARS-CoV-2.
Keywords:
- COVID-19
- pomegranate
- polyphenols
- acute respiratory distress syndrome
- flavonoids
How to Cite
Amarasekara, D. D. N., Ratnayake, I. A., Wewalwela, J. J., & Gamage, W. U. N. (2022). Therapeutic Potential of Pomegranate in SARS-CoV-2 and Acute Respiratory Distress Syndrome (ARDS). European Journal of Medicinal Plants, 33(12), 1-16. https://doi.org/10.9734/ejmp/2022/v33i121109
References
Shi Y, Wang G, Cai XP, Deng JW, Zheng L, Zhu HH et al. An overview of COVID-19. J Zhejiang Univ Sci B. 2020;21(5):343-60.
Anonymous. WHO Coronavirus (COVID-19) Dashboard, on. World Health Organization; 27.9.2021 [cited 27.9.2021]. Available from: https://covid19.who.int/.
Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed. 2020;91(1):157-60.
Guzzi PH, Mercatelli D, Ceraolo C, Giorgi FM. Master regulator analysis of the SARS-CoV-2/human interactome. J Clin Med. 2020;9(4).
Zhou G, Chen S, Chen Z. Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies. Front Med. 2020;14(2):117-25.
Fung TS, Liu DX. Human coronavirus: Host-Pathogen Interaction. Annu Rev Microbiol. 2019;73:529-57.
Alene M, Yismaw L, Assemie MA, Ketema DB, Gietaneh W, Birhan TY. Serial interval and incubation period of COVID-19: a systematic review and meta-analysis. BMC Infect Dis. 2021;21(1):257.
Tzotzos SJ, Fischer B, Fischer H, Zeitlinger M. Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey. Crit Care. 2020;24(1):516.
Chilamakuri R, Agarwal S. COVID-19: characteristics and therapeutics. Cells. 2021;10(2):206.
Anonymous. Antiviral Drugs That Are Approved, Authorized, or Under Evaluation for the Treatment of COVID-19: National Institutes of Health 2022 [cited 2022 17.10.2022]. Available:https://www.covid19treatmentguidelines.nih.gov/ therapies/antiviral-therapy/summary-recommendations/.
Anonymous. Emergency use authorization; 2021 [cited 25.8.2021].
Available:https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs
Thangavelu A, Elavarasu S, Sundaram R, Kumar T, Rajendran D, Prem F. Ancient seed for modern cure - pomegranate review of therapeutic applications in periodontics. J Pharm Bioallied Sci. 2017;9(Suppl 1):S11-4.
Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009;2(5):270-8.
Rettig MB, Heber D, An J, Seeram NP, Rao JY, Liu H et al. Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism. Mol Cancer Ther. 2008;7(9):2662-71.
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001;74(4):418-25.
Khoo HE, Azlan A, Tang ST, Lim SM. Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food Nutr Res. 2017; 61(1):1361779.
Akhtar S, Ismail T, Fraternale D, Sestili P. Pomegranate peel and peel extracts: chemistry and food features. Food Chem. 2015;174:417-25.
Venkata CKS, Prakash S, Prakash I. Bioactive chemical constituents from pomegranate (Punica granatum) juice, seed and peel-A review in p, editor.
Sreekumar S, Sithul H, Muraleedharan P, Azeez JM, Sreeharshan S. Pomegranate fruit as a rich source of biologically active compounds. BioMed Res Int. 2014;2014:686921.
Millet JK, Whittaker GR. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res. 2015;202:120-34.
Ragia G, Manolopoulos VG. Inhibition of SARS-CoV-2 entry through the ACE2/TMPRSS2 pathway: a promising approach for uncovering early COVID-19 drug therapies. Eur J Clin Pharmacol. 2020;76(12):1623-30.
Chikhale RV, Gupta VK, Eldesoky GE, Wabaidur SM, Patil SA, Islam MA. Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies. J Biomol Struct Dyn. 2020:1-16.
Zhao X, Yuan Z, Fang Y, Yin Y, Feng L. Flavonols and flavones changes in pomegranate (Punica granatum L.) fruit peel during fruit development. J Agric Sci Technol. 2014;16:1649-59.
Adaramoye O, Erguen B, Nitzsche B, Höpfner M, Jung K, Rabien A. Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cells. Chem Biol Interact. 2017;274:100-6.
Johnson BA, Xie X, Kalveram B, Lokugamage KG, Muruato A, Zou J et al. Furin Cleavage Site Is Key to SARS-CoV-2 Pathogenesis. bioRxiv: The preprint server for biology; 2020.
Wu C, Zheng M, Yang Y, Gu X, Yang K, Li M et al. Furin: A potential therapeutic target for COVID-19. iScience. 2020; 23(10):101642.
Zhu J, Van de Ven WJM, Verbiest T, Koeckelberghs G, Chen C, Cui Y et al. Polyphenols can inhibit Furin in vitro as A result of the reactivity of their auto-oxidation products to proteins. Curr Med Chem. 2013;20(6):840-50.
Bosch BJ, Bartelink W, Rottier PJM. Cathepsin L functionally cleaves the severe acute respiratory syndrome coronavirus class I fusion protein upstream of rather than adjacent to the fusion peptide. J Virol. 2008;82(17):8887-90.
Liu T, Luo S, Libby P, Shi GP. Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients. Pharmacol Ther. 2020;213: 107587.
de Sousa LRF, Wu H, Nebo L, Fernandes JB, da Silva MFdGF, Kiefer W et al. Natural products as inhibitors of recombinant cathepsin L of Leishmania mexicana. Exp Parasitol. 2015;156:42-8.
Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110(6):673-87.
Sigrist CJ, Bridge A, Le Mercier P. A potential role for integrins in host cell entry by SARS-CoV-2. Antiviral Res. 2020; 177:104759.
Dakal TC. SARS-CoV-2 attachment to host cells is possibly mediated via RGD-integrin interaction in a calcium-dependent manner and suggests pulmonary EDTA chelation therapy as a novel treatment for COVID 19. Immunobiology. 2021;226(1):152021.
Lim W, Song G. Inhibitory effects of delphinidin on the proliferation of ovarian cancer cells via PI3K/AKT and ERK 1/2 MAPK signal transduction. Oncol Lett. 2017;14(1):810-8.
Rahimi HR, Arastoo M, Ostad SN. A comprehensive review of Punica granatum (pomegranate) properties in toxicological, pharmacological, cellular and molecular biology researches. Iran J Pharm Res. 2012;11(2):385-400.
Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586-90.
Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76:14-20.
Pang J, Xu F, Aondio G, Li Y, Fumagalli A, Lu M et al. Efficacy and tolerability of bevacizumab in patients with severe COVID-19. Nat Commun. 2021;12(1):814.
Song P, Li W, Xie J, Hou Y, You C. Cytokine storm induced by SARS-CoV-2. Clin Chim Acta. 2020;509:280-7.
Xiong Y, Liu Y, Cao L, Wang D, Guo M, Jiang A et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg Microbes Infect. 2020;9(1):761-70.
Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020;53:25-32.
Peiris JSM, Chu CM, Cheng VCC, Chan KS, Hung IFN, Poon LLM et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767-72..
Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M et al. How COVID-19 induces cytokine storm with high mortality. Inflam Regen. 2020;40:37.
Grommes J, Soehnlein O. Contribution of neutrophils to acute lung injury. Mol Med. 2011;17(3-4):293-307.
Gubernatorova EO, Gorshkova EA, Polinova AI, Drutskaya MS. IL-6: relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 2020;53: 13-24.
Liao QJ, Ye LB, Timani KA, Zeng YC, She YL, Ye L et al. Activation of NF-kappaB by the full-length nucleocapsid protein of the SARS coronavirus. Acta Biochim Biophys Sin (Shanghai). 2005;37(9):607-12.
Ivanisenko NV, Seyrek K, Kolchanov NA, Ivanisenko VA, Lavrik IN. The role of death domain proteins in host response upon SARS-CoV-2 infection: modulation of programmed cell death and translational applications. Cell Death Discov. 2020;6(1):101.
Kircheis R, Haasbach E, Lueftenegger D, Heyken WT, Ocker M, Planz O. NF-κB pathway as a potential target for treatment of critical stage COVID-19 patients. Front Immunol. 2020;11:598444.
DeDiego ML, Nieto-Torres JL, Regla-Nava JA, Jimenez-Guardeño JM, Fernandez-Delgado R, Fett C et al. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2014; 88(2):913-24.
Hariharan A, Hakeem AR, Radhakrishnan S, Reddy MS, Rela M. The role and therapeutic potential of NF-kappa-B pathway in severe COVID-19 patients. Inflammopharmacology. 2021;29(1):91-100.
Heber D. Pomegranate ellagitannins. Copyright, Herbal Medicine: Biomolecular and Clinical Aspects. CRC Press/Taylor & Francis. 2011.
Cao Y, Chen J, Ren G, Zhang Y, Tan X, Yang L. Punicalagin prevents inflammation in LPS-induced RAW264.7 macrophages by inhibiting FoxO3a/Autophagy signaling pathway. Nutrients. 2019;11(11).
Kim BH, Choi JS, Yi EH, Lee JK, Won C, Ye SK et al. Relative antioxidant activities of quercetin and its structurally related substances and their effects on NF-κB/CRE/AP-1 signaling in murine macrophages. Mol Cells. 2013;35(5):410-20.
Kim JY, Hildebrandt MA, Pu X, Ye Y, Correa AM, Vaporciyan AA, et al. Variations in the vascular endothelial growth factor pathway predict pulmonary complications. Ann Thorac Surg. 2012;94(4):1079-84; discussion 1084-5.
Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP. The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. Eur Respir J. 2014;43(1):276-85.
Turkia M. COVID-19, vascular endothelial growth factor (VEGF) and iodide In p, editor.
Aboonabi A, Rahmat A, Othman F. Antioxidant effect of pomegranate against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Toxicol Rep. 2014;1:915-22.
Lamy S, Blanchette M, Michaud-Levesque J, Lafleur R, Durocher Y, Moghrabi A et al. Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation. Carcinogenesis. 2006;27(5):989-96.
Dana N, Javanmard ShH, Rafiee L. Antiangiogenic and antiproliferative effects of black pomegranate peel extract on melanoma cell line. Res Pharm Sci. 2015;10(2):117-24.
Fligiel SE, Standiford T, Fligiel HM, Tashkin D, Strieter RM, Warner RL et al. Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung injury. Hum Pathol. 2006;37(4):422-30.
Steinberg J, Halter J, Schiller HJ, Dasilva M, Landas S, Gatto LA et al. Metalloproteinase inhibition reduces lung injury and improves survival after cecal ligation and puncture in rats. J Surg Res. 2003;111(2):185-95.
Nagase H, Sasaki K, Kito H, Haga A, Sato T. Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro. Planta Med. 1998;64(3):216-9.
Coates EM, Popa G, Gill CI, McCann MJ, McDougall GJ, Stewart D et al. Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer. J Carcinog. 2007;6:4.
Negri A, Naponelli V, Rizzi F, Bettuzzi S. Molecular targets of epigallocatechin-gallate (EGCG): A special focus on signal transduction and cancer. Nutrients. 2018;10(12).
Hanudel MR, Zinter MS, Chen L, Gala K, Lim M, Guglielmo M et al. Plasma total fibroblast growth factor 23 levels are associated with acute kidney injury and mortality in children with acute respiratory distress syndrome. PLOS ONE. 2019;14(9):e0222065.
Grimminger F, Günther A, Vancheri C. The role of tyrosine kinases in the pathogenesis of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1426-33.
George PM, Wells AU, Jenkins RG. Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir Med. 2020;8(8):807-15.
Mizutani T, Fukushi S, Saijo M, Kurane I, Morikawa S. Phosphorylation of p38 MAPK and its downstream targets in SARS coronavirus-infected cells. Biochem Biophys Res Commun. 2004;319(4):1228-34.
Kono M, Tatsumi K, Imai AM, Saito K, Kuriyama T, Shirasawa H. Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: involvement of p38 MAPK and ERK. Antiviral Res. 2008;77(2): 150-2.
Grimes JM, Grimes KV. p38 MAPK inhibition: A promising therapeutic approach for COVID-19. J Mol Cell Cardiol. 2020;144:63-5.
Afaq F, Malik A, Syed D, Maes D, Matsui MS, Mukhtar H. Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes paragraph sign. Photochem Photobiol. 2005;81(1):38-45.
Rasheed Z, Akhtar N, Haqqi TM. Pomegranate extract inhibits the interleukin-1β-induced activation of MKK-3, p38α-MAPK and transcription factor RUNX-2 in human osteoarthritis chondrocytes. Arthritis Res Ther. 2010;12(5):R195.
Wong HH, Kumar P, Tay FP, Moreau D, Liu DX, Bard F. Genome-wide screen reveals valosin-containing protein requirement for coronavirus exit from endosomes. J Virol. 2015;89(21):11116-28.
Dominguez Andres A, Feng Y, Campos AR, Yin J, Yang C-C, James B et al. SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells. bioRxiv: The preprint server for biology; n2020.
Kroeger N, Belldegrun AS, Pantuck AJ. J P. Pomegranate Extracts in the Management of Men’s Urologic Health: Scientific Rationale and Preclinical and Clinical Data. Evid Based Complement Alternat Med. 2013;2013:701434.
Lee ST, Wu YL, Chien LH, Chen ST, Tzeng YK, Wu TF. Proteomic exploration of the impacts of pomegranate fruit juice on the global gene expression of prostate cancer cell. Proteomics. 2012;12(21):3251-62.
Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020; 17(5):533-5.
Kamiya T, Seow SV, Wong D, Robinson M, Campana D. Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells. J Clin Invest. 2019;129(5):2094-106.
Altieri F, Cairone F, Giamogante F, Carradori S, Locatelli M, Chichiarelli S, et al. Influence of ellagitannins extracted by pomegranate fruit on disulfide isomerase PDIA3 activity. Nutrients. 2019; 11(1):186.
Seeram N, Lee R, Hardy M, Heber D. Rapid large scale purification of ellagitannins from pomegranate husk, a by-product of the commercial juice industry. Sep Purif Technol. 2005;41(1): 49-55.
Turrini E, Ferruzzi L, Fimognari C. Potential effects of pomegranate polyphenols in cancer prevention and therapy. Oxid Med Cell Longev. 2015;2015:938475..
Yao X, Cheng X, Zhang L, Yu H, Bao J, Guan H et al. Punicalagin from pomegranate promotes human papillary thyroid carcinoma BCPAP cell death by triggering ATM-mediated DNA damage response. Nutr Res. 2017;47: 63-71.
Yu CS, Lai KC, Yang JS, Chiang JH, Lu CC, Wu CL et al. Quercetin inhibited murine leukemia WEHI-3 cells in vivo and promoted immune response. Phytother Res. 2010;24(2):163-8.
Kim YH, Won YS, Yang X, Kumazoe M, Yamashita S, Hara A et al. Green tea catechin metabolites exert immunoregulatory effects on CD4(+) T cell and natural killer cell activities. J Agric Food Chem. 2016;64(18):3591-7.
Young LS, Dawson CW, Eliopoulos AG. Viruses and apoptosis. Br Med Bull. 1997;53(3):509-21.
Hay S, Kannourakis G. A time to kill: viral manipulation of the cell death program. J Gen Virol. 2002;83(7):1547-64.
Li J, Wang G, Hou C, Li J, Luo Y, Li B. Punicalagin and ellagic acid from pomegranate peel induce apoptosis and inhibits proliferation in human HepG2 hepatoma cells through targeting mitochondria. Food Agric Immunol. 2019;30(1):897-912.
Malik A, Afaq S, Shahid M, Akhtar K, Assiri A. Influence of ellagic acid on prostate cancer cell proliferation: a caspase-dependent pathway. Asian Pac J Trop Med. 2011;4(7):550-5..
Wu P, Meng X, Zheng H, Zeng Q, Chen T, Wang W et al. Kaempferol attenuates ROS-induced hemolysis and the molecular mechanism of its induction of apoptosis on bladder cancer. Molecules. 2018;23(10):2592.
Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets. 2008;8(7):634-46.
Bordi L, Castilletti C, Falasca L, Ciccosanti F, Calcaterra S, Rozera G et al. Bcl-2 inhibits the caspase-dependent apoptosis induced by SARS-CoV without affecting virus replication kinetics. Arch Virol. 2006;151(2):369-77.
Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci U S A. 2005;102(41):14813-8.
Ma-Lauer Y, Carbajo-Lozoya J, Hein MY, Müller MA, Deng W, Lei J et al. p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1pro via E3 ubiquitin ligase RCHY1. Proc Natl Acad Sci U S A. 2016;113(35):E5192-201.
Millar FR, Summers C, Griffiths MJ, Toshner MR, Proudfoot AG. The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities. Thorax. 2016;71(5):462-73.
Maas SL, Soehnlein O, Viola JR. Organ-specific mechanisms of transendothelial neutrophil migration in the lung, liver, kidney, and aorta. Front Immunol. 2018;9:2739.
Hidalgo M, Martin-Santamaria S, Recio I, Sanchez-Moreno C, de Pascual-Teresa B, Rimbach G et al. Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites. Genes Nutr. 2012;7(2):295-306.
Rios-Corripio G, Guerrero-Beltrán JÁ. Antioxidant and physicochemical characteristics of unfermented and fermented pomegranate (Punica granatum L.) beverages. J Food Sci Technol. 2019;56(1):132-9..
Feng Z, Zhaohe Y, Xueqing Z, Yanlei Y, Lijuan F. Composition and contents of anthocyanins in different pomegranate cultivars (ed), International Society for Horticultural Science (ISHS). Acta Hortic. 2015;(1089):35-41..
Wang C, Xie J, Zhao L, Fei X, Zhang H, Tan Y et al. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. EBiomedicine. 2020;57:102833.
Abubakar E-MM. Antibacterial efficacy of stem bark extracts of Mangifera indica against some bacteria associated with respiratory tract infections. Sci Res Essays. 2009;4:1031-7.
Vidyadhara S, Sasidhar R, Deepti B, Wilwin E, Sowjanyalakshmi B. Formulation and evaluation of amoxicillin trihydrate lozenges. Dhaka Univ J Pharm Sci. 2015;14(1):61-70.
Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q et al. Emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: Biology and therapeutic options. J Clin Microbiol. 2020;58(5):e00187-20.
Kumar A, Kubota Y, Chernov M, Kasuya H. Potential role of zinc supplementation in prophylaxis and treatment of COVID-19. Med Hypotheses. 2020;144:109848.
Dabbagh-Bazarbachi H, Clergeaud G, Quesada IM, Ortiz M, O’Sullivan CK, Fernández-Larrea JB. Zinc ionophore activity of quercetin and epigallocatechin-gallate: from hepa 1-6 cells to a liposome model. J Agric Food Chem. 2014;62(32):8085-93.
Hwang MK, Kang NJ, Heo YS, Lee KW, Lee HJ. Fyn kinase is a direct molecular target of delphinidin for the inhibition of cyclooxygenase-2 expression induced by tumor necrosis factor-α. Biochem Pharmacol. 2009;77(7):1213-22.
Formiga FR, Leblanc R, de Souza Rebouças J, Farias LP, de Oliveira RN, Pena L. Ivermectin: an award-winning drug with expected antiviral activity against COVID-19. J Control Release. 2021;329:758-61.
Shin JS, Jung E, Kim M, Baric RS, Go YY. Saracatinib inhibits Middle East respiratory syndrome-coronavirus replication in vitro. Viruses. 2018;10(6):283.
Ghasemnejad-Berenji M, Pashapour S. SARS-CoV-2 and the possible role of Raf/MEK/ERK pathway in viral survival: is this a potential therapeutic strategy for COVID-19? Pharmacology. 2021;106 (1-2):119-22.
Chen XY, Zhou J, Luo LP, Han B, Li F, Chen JY et al. Black rice anthocyanins suppress metastasis of breast cancer cells by targeting RAS/RAF/MAPK pathway. BioMed Res Int. 2015;2015:414250.
Magangana TP, Makunga NP, Fawole OA, Opara UL. Processing factors affecting the phytochemical and nutritional properties of pomegranate (Punica granatum L.) peel waste: a review. Molecules. 2020;25(20): 4690.
Babu PVA, Liu D. Green tea catechins and cardiovascular health: an update. Curr Med Chem. 2008;15(18):1840-50.
Zhang L, Deng M, Zhou S. Tetramethylpyrazine inhibits hypoxia-induced pulmonary vascular leakage in rats via the ROS-HIF-VEGF pathway. Pharmacology. 2011;87(5-6): 265-73.
Marchetti M. COVID-19-driven endothelial damage: complement, HIF-1, and ABL2 are potential pathways of damage and targets for cure. Ann Hematol. 2020;99(8):1701-7.
Zhou J, Liao W, Yang J, Ma K, Li X, Wang Y et al. FOXO3 induces FOXO1-dependent autophagy by activating the AKT1 signaling pathway. Autophagy. 2012;8(12):1712-23.
Shojaei S, Suresh M, Klionsky DJ, Labouta HI, Ghavami S. Autophagy and SARS-CoV-2 infection: Apossible smart targeting of the autophagy pathway. Virulence. 2020;11(1):805-10.
Farag RS, Abdel-Latif MS, Emam SS, Tawfeek SH. Phytochemical screening and polyphenol constituents of pomegranate peels and leave juices In p, editor.
Anonymous. WHO Coronavirus (COVID-19) Dashboard, on. World Health Organization; 27.9.2021 [cited 27.9.2021]. Available from: https://covid19.who.int/.
Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed. 2020;91(1):157-60.
Guzzi PH, Mercatelli D, Ceraolo C, Giorgi FM. Master regulator analysis of the SARS-CoV-2/human interactome. J Clin Med. 2020;9(4).
Zhou G, Chen S, Chen Z. Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies. Front Med. 2020;14(2):117-25.
Fung TS, Liu DX. Human coronavirus: Host-Pathogen Interaction. Annu Rev Microbiol. 2019;73:529-57.
Alene M, Yismaw L, Assemie MA, Ketema DB, Gietaneh W, Birhan TY. Serial interval and incubation period of COVID-19: a systematic review and meta-analysis. BMC Infect Dis. 2021;21(1):257.
Tzotzos SJ, Fischer B, Fischer H, Zeitlinger M. Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey. Crit Care. 2020;24(1):516.
Chilamakuri R, Agarwal S. COVID-19: characteristics and therapeutics. Cells. 2021;10(2):206.
Anonymous. Antiviral Drugs That Are Approved, Authorized, or Under Evaluation for the Treatment of COVID-19: National Institutes of Health 2022 [cited 2022 17.10.2022]. Available:https://www.covid19treatmentguidelines.nih.gov/ therapies/antiviral-therapy/summary-recommendations/.
Anonymous. Emergency use authorization; 2021 [cited 25.8.2021].
Available:https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs
Thangavelu A, Elavarasu S, Sundaram R, Kumar T, Rajendran D, Prem F. Ancient seed for modern cure - pomegranate review of therapeutic applications in periodontics. J Pharm Bioallied Sci. 2017;9(Suppl 1):S11-4.
Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009;2(5):270-8.
Rettig MB, Heber D, An J, Seeram NP, Rao JY, Liu H et al. Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism. Mol Cancer Ther. 2008;7(9):2662-71.
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001;74(4):418-25.
Khoo HE, Azlan A, Tang ST, Lim SM. Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food Nutr Res. 2017; 61(1):1361779.
Akhtar S, Ismail T, Fraternale D, Sestili P. Pomegranate peel and peel extracts: chemistry and food features. Food Chem. 2015;174:417-25.
Venkata CKS, Prakash S, Prakash I. Bioactive chemical constituents from pomegranate (Punica granatum) juice, seed and peel-A review in p, editor.
Sreekumar S, Sithul H, Muraleedharan P, Azeez JM, Sreeharshan S. Pomegranate fruit as a rich source of biologically active compounds. BioMed Res Int. 2014;2014:686921.
Millet JK, Whittaker GR. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res. 2015;202:120-34.
Ragia G, Manolopoulos VG. Inhibition of SARS-CoV-2 entry through the ACE2/TMPRSS2 pathway: a promising approach for uncovering early COVID-19 drug therapies. Eur J Clin Pharmacol. 2020;76(12):1623-30.
Chikhale RV, Gupta VK, Eldesoky GE, Wabaidur SM, Patil SA, Islam MA. Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies. J Biomol Struct Dyn. 2020:1-16.
Zhao X, Yuan Z, Fang Y, Yin Y, Feng L. Flavonols and flavones changes in pomegranate (Punica granatum L.) fruit peel during fruit development. J Agric Sci Technol. 2014;16:1649-59.
Adaramoye O, Erguen B, Nitzsche B, Höpfner M, Jung K, Rabien A. Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cells. Chem Biol Interact. 2017;274:100-6.
Johnson BA, Xie X, Kalveram B, Lokugamage KG, Muruato A, Zou J et al. Furin Cleavage Site Is Key to SARS-CoV-2 Pathogenesis. bioRxiv: The preprint server for biology; 2020.
Wu C, Zheng M, Yang Y, Gu X, Yang K, Li M et al. Furin: A potential therapeutic target for COVID-19. iScience. 2020; 23(10):101642.
Zhu J, Van de Ven WJM, Verbiest T, Koeckelberghs G, Chen C, Cui Y et al. Polyphenols can inhibit Furin in vitro as A result of the reactivity of their auto-oxidation products to proteins. Curr Med Chem. 2013;20(6):840-50.
Bosch BJ, Bartelink W, Rottier PJM. Cathepsin L functionally cleaves the severe acute respiratory syndrome coronavirus class I fusion protein upstream of rather than adjacent to the fusion peptide. J Virol. 2008;82(17):8887-90.
Liu T, Luo S, Libby P, Shi GP. Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients. Pharmacol Ther. 2020;213: 107587.
de Sousa LRF, Wu H, Nebo L, Fernandes JB, da Silva MFdGF, Kiefer W et al. Natural products as inhibitors of recombinant cathepsin L of Leishmania mexicana. Exp Parasitol. 2015;156:42-8.
Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110(6):673-87.
Sigrist CJ, Bridge A, Le Mercier P. A potential role for integrins in host cell entry by SARS-CoV-2. Antiviral Res. 2020; 177:104759.
Dakal TC. SARS-CoV-2 attachment to host cells is possibly mediated via RGD-integrin interaction in a calcium-dependent manner and suggests pulmonary EDTA chelation therapy as a novel treatment for COVID 19. Immunobiology. 2021;226(1):152021.
Lim W, Song G. Inhibitory effects of delphinidin on the proliferation of ovarian cancer cells via PI3K/AKT and ERK 1/2 MAPK signal transduction. Oncol Lett. 2017;14(1):810-8.
Rahimi HR, Arastoo M, Ostad SN. A comprehensive review of Punica granatum (pomegranate) properties in toxicological, pharmacological, cellular and molecular biology researches. Iran J Pharm Res. 2012;11(2):385-400.
Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586-90.
Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76:14-20.
Pang J, Xu F, Aondio G, Li Y, Fumagalli A, Lu M et al. Efficacy and tolerability of bevacizumab in patients with severe COVID-19. Nat Commun. 2021;12(1):814.
Song P, Li W, Xie J, Hou Y, You C. Cytokine storm induced by SARS-CoV-2. Clin Chim Acta. 2020;509:280-7.
Xiong Y, Liu Y, Cao L, Wang D, Guo M, Jiang A et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg Microbes Infect. 2020;9(1):761-70.
Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020;53:25-32.
Peiris JSM, Chu CM, Cheng VCC, Chan KS, Hung IFN, Poon LLM et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767-72..
Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M et al. How COVID-19 induces cytokine storm with high mortality. Inflam Regen. 2020;40:37.
Grommes J, Soehnlein O. Contribution of neutrophils to acute lung injury. Mol Med. 2011;17(3-4):293-307.
Gubernatorova EO, Gorshkova EA, Polinova AI, Drutskaya MS. IL-6: relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 2020;53: 13-24.
Liao QJ, Ye LB, Timani KA, Zeng YC, She YL, Ye L et al. Activation of NF-kappaB by the full-length nucleocapsid protein of the SARS coronavirus. Acta Biochim Biophys Sin (Shanghai). 2005;37(9):607-12.
Ivanisenko NV, Seyrek K, Kolchanov NA, Ivanisenko VA, Lavrik IN. The role of death domain proteins in host response upon SARS-CoV-2 infection: modulation of programmed cell death and translational applications. Cell Death Discov. 2020;6(1):101.
Kircheis R, Haasbach E, Lueftenegger D, Heyken WT, Ocker M, Planz O. NF-κB pathway as a potential target for treatment of critical stage COVID-19 patients. Front Immunol. 2020;11:598444.
DeDiego ML, Nieto-Torres JL, Regla-Nava JA, Jimenez-Guardeño JM, Fernandez-Delgado R, Fett C et al. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2014; 88(2):913-24.
Hariharan A, Hakeem AR, Radhakrishnan S, Reddy MS, Rela M. The role and therapeutic potential of NF-kappa-B pathway in severe COVID-19 patients. Inflammopharmacology. 2021;29(1):91-100.
Heber D. Pomegranate ellagitannins. Copyright, Herbal Medicine: Biomolecular and Clinical Aspects. CRC Press/Taylor & Francis. 2011.
Cao Y, Chen J, Ren G, Zhang Y, Tan X, Yang L. Punicalagin prevents inflammation in LPS-induced RAW264.7 macrophages by inhibiting FoxO3a/Autophagy signaling pathway. Nutrients. 2019;11(11).
Kim BH, Choi JS, Yi EH, Lee JK, Won C, Ye SK et al. Relative antioxidant activities of quercetin and its structurally related substances and their effects on NF-κB/CRE/AP-1 signaling in murine macrophages. Mol Cells. 2013;35(5):410-20.
Kim JY, Hildebrandt MA, Pu X, Ye Y, Correa AM, Vaporciyan AA, et al. Variations in the vascular endothelial growth factor pathway predict pulmonary complications. Ann Thorac Surg. 2012;94(4):1079-84; discussion 1084-5.
Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP. The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. Eur Respir J. 2014;43(1):276-85.
Turkia M. COVID-19, vascular endothelial growth factor (VEGF) and iodide In p, editor.
Aboonabi A, Rahmat A, Othman F. Antioxidant effect of pomegranate against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Toxicol Rep. 2014;1:915-22.
Lamy S, Blanchette M, Michaud-Levesque J, Lafleur R, Durocher Y, Moghrabi A et al. Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation. Carcinogenesis. 2006;27(5):989-96.
Dana N, Javanmard ShH, Rafiee L. Antiangiogenic and antiproliferative effects of black pomegranate peel extract on melanoma cell line. Res Pharm Sci. 2015;10(2):117-24.
Fligiel SE, Standiford T, Fligiel HM, Tashkin D, Strieter RM, Warner RL et al. Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung injury. Hum Pathol. 2006;37(4):422-30.
Steinberg J, Halter J, Schiller HJ, Dasilva M, Landas S, Gatto LA et al. Metalloproteinase inhibition reduces lung injury and improves survival after cecal ligation and puncture in rats. J Surg Res. 2003;111(2):185-95.
Nagase H, Sasaki K, Kito H, Haga A, Sato T. Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro. Planta Med. 1998;64(3):216-9.
Coates EM, Popa G, Gill CI, McCann MJ, McDougall GJ, Stewart D et al. Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer. J Carcinog. 2007;6:4.
Negri A, Naponelli V, Rizzi F, Bettuzzi S. Molecular targets of epigallocatechin-gallate (EGCG): A special focus on signal transduction and cancer. Nutrients. 2018;10(12).
Hanudel MR, Zinter MS, Chen L, Gala K, Lim M, Guglielmo M et al. Plasma total fibroblast growth factor 23 levels are associated with acute kidney injury and mortality in children with acute respiratory distress syndrome. PLOS ONE. 2019;14(9):e0222065.
Grimminger F, Günther A, Vancheri C. The role of tyrosine kinases in the pathogenesis of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1426-33.
George PM, Wells AU, Jenkins RG. Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir Med. 2020;8(8):807-15.
Mizutani T, Fukushi S, Saijo M, Kurane I, Morikawa S. Phosphorylation of p38 MAPK and its downstream targets in SARS coronavirus-infected cells. Biochem Biophys Res Commun. 2004;319(4):1228-34.
Kono M, Tatsumi K, Imai AM, Saito K, Kuriyama T, Shirasawa H. Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: involvement of p38 MAPK and ERK. Antiviral Res. 2008;77(2): 150-2.
Grimes JM, Grimes KV. p38 MAPK inhibition: A promising therapeutic approach for COVID-19. J Mol Cell Cardiol. 2020;144:63-5.
Afaq F, Malik A, Syed D, Maes D, Matsui MS, Mukhtar H. Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes paragraph sign. Photochem Photobiol. 2005;81(1):38-45.
Rasheed Z, Akhtar N, Haqqi TM. Pomegranate extract inhibits the interleukin-1β-induced activation of MKK-3, p38α-MAPK and transcription factor RUNX-2 in human osteoarthritis chondrocytes. Arthritis Res Ther. 2010;12(5):R195.
Wong HH, Kumar P, Tay FP, Moreau D, Liu DX, Bard F. Genome-wide screen reveals valosin-containing protein requirement for coronavirus exit from endosomes. J Virol. 2015;89(21):11116-28.
Dominguez Andres A, Feng Y, Campos AR, Yin J, Yang C-C, James B et al. SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells. bioRxiv: The preprint server for biology; n2020.
Kroeger N, Belldegrun AS, Pantuck AJ. J P. Pomegranate Extracts in the Management of Men’s Urologic Health: Scientific Rationale and Preclinical and Clinical Data. Evid Based Complement Alternat Med. 2013;2013:701434.
Lee ST, Wu YL, Chien LH, Chen ST, Tzeng YK, Wu TF. Proteomic exploration of the impacts of pomegranate fruit juice on the global gene expression of prostate cancer cell. Proteomics. 2012;12(21):3251-62.
Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020; 17(5):533-5.
Kamiya T, Seow SV, Wong D, Robinson M, Campana D. Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells. J Clin Invest. 2019;129(5):2094-106.
Altieri F, Cairone F, Giamogante F, Carradori S, Locatelli M, Chichiarelli S, et al. Influence of ellagitannins extracted by pomegranate fruit on disulfide isomerase PDIA3 activity. Nutrients. 2019; 11(1):186.
Seeram N, Lee R, Hardy M, Heber D. Rapid large scale purification of ellagitannins from pomegranate husk, a by-product of the commercial juice industry. Sep Purif Technol. 2005;41(1): 49-55.
Turrini E, Ferruzzi L, Fimognari C. Potential effects of pomegranate polyphenols in cancer prevention and therapy. Oxid Med Cell Longev. 2015;2015:938475..
Yao X, Cheng X, Zhang L, Yu H, Bao J, Guan H et al. Punicalagin from pomegranate promotes human papillary thyroid carcinoma BCPAP cell death by triggering ATM-mediated DNA damage response. Nutr Res. 2017;47: 63-71.
Yu CS, Lai KC, Yang JS, Chiang JH, Lu CC, Wu CL et al. Quercetin inhibited murine leukemia WEHI-3 cells in vivo and promoted immune response. Phytother Res. 2010;24(2):163-8.
Kim YH, Won YS, Yang X, Kumazoe M, Yamashita S, Hara A et al. Green tea catechin metabolites exert immunoregulatory effects on CD4(+) T cell and natural killer cell activities. J Agric Food Chem. 2016;64(18):3591-7.
Young LS, Dawson CW, Eliopoulos AG. Viruses and apoptosis. Br Med Bull. 1997;53(3):509-21.
Hay S, Kannourakis G. A time to kill: viral manipulation of the cell death program. J Gen Virol. 2002;83(7):1547-64.
Li J, Wang G, Hou C, Li J, Luo Y, Li B. Punicalagin and ellagic acid from pomegranate peel induce apoptosis and inhibits proliferation in human HepG2 hepatoma cells through targeting mitochondria. Food Agric Immunol. 2019;30(1):897-912.
Malik A, Afaq S, Shahid M, Akhtar K, Assiri A. Influence of ellagic acid on prostate cancer cell proliferation: a caspase-dependent pathway. Asian Pac J Trop Med. 2011;4(7):550-5..
Wu P, Meng X, Zheng H, Zeng Q, Chen T, Wang W et al. Kaempferol attenuates ROS-induced hemolysis and the molecular mechanism of its induction of apoptosis on bladder cancer. Molecules. 2018;23(10):2592.
Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets. 2008;8(7):634-46.
Bordi L, Castilletti C, Falasca L, Ciccosanti F, Calcaterra S, Rozera G et al. Bcl-2 inhibits the caspase-dependent apoptosis induced by SARS-CoV without affecting virus replication kinetics. Arch Virol. 2006;151(2):369-77.
Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci U S A. 2005;102(41):14813-8.
Ma-Lauer Y, Carbajo-Lozoya J, Hein MY, Müller MA, Deng W, Lei J et al. p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1pro via E3 ubiquitin ligase RCHY1. Proc Natl Acad Sci U S A. 2016;113(35):E5192-201.
Millar FR, Summers C, Griffiths MJ, Toshner MR, Proudfoot AG. The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities. Thorax. 2016;71(5):462-73.
Maas SL, Soehnlein O, Viola JR. Organ-specific mechanisms of transendothelial neutrophil migration in the lung, liver, kidney, and aorta. Front Immunol. 2018;9:2739.
Hidalgo M, Martin-Santamaria S, Recio I, Sanchez-Moreno C, de Pascual-Teresa B, Rimbach G et al. Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites. Genes Nutr. 2012;7(2):295-306.
Rios-Corripio G, Guerrero-Beltrán JÁ. Antioxidant and physicochemical characteristics of unfermented and fermented pomegranate (Punica granatum L.) beverages. J Food Sci Technol. 2019;56(1):132-9..
Feng Z, Zhaohe Y, Xueqing Z, Yanlei Y, Lijuan F. Composition and contents of anthocyanins in different pomegranate cultivars (ed), International Society for Horticultural Science (ISHS). Acta Hortic. 2015;(1089):35-41..
Wang C, Xie J, Zhao L, Fei X, Zhang H, Tan Y et al. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. EBiomedicine. 2020;57:102833.
Abubakar E-MM. Antibacterial efficacy of stem bark extracts of Mangifera indica against some bacteria associated with respiratory tract infections. Sci Res Essays. 2009;4:1031-7.
Vidyadhara S, Sasidhar R, Deepti B, Wilwin E, Sowjanyalakshmi B. Formulation and evaluation of amoxicillin trihydrate lozenges. Dhaka Univ J Pharm Sci. 2015;14(1):61-70.
Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q et al. Emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: Biology and therapeutic options. J Clin Microbiol. 2020;58(5):e00187-20.
Kumar A, Kubota Y, Chernov M, Kasuya H. Potential role of zinc supplementation in prophylaxis and treatment of COVID-19. Med Hypotheses. 2020;144:109848.
Dabbagh-Bazarbachi H, Clergeaud G, Quesada IM, Ortiz M, O’Sullivan CK, Fernández-Larrea JB. Zinc ionophore activity of quercetin and epigallocatechin-gallate: from hepa 1-6 cells to a liposome model. J Agric Food Chem. 2014;62(32):8085-93.
Hwang MK, Kang NJ, Heo YS, Lee KW, Lee HJ. Fyn kinase is a direct molecular target of delphinidin for the inhibition of cyclooxygenase-2 expression induced by tumor necrosis factor-α. Biochem Pharmacol. 2009;77(7):1213-22.
Formiga FR, Leblanc R, de Souza Rebouças J, Farias LP, de Oliveira RN, Pena L. Ivermectin: an award-winning drug with expected antiviral activity against COVID-19. J Control Release. 2021;329:758-61.
Shin JS, Jung E, Kim M, Baric RS, Go YY. Saracatinib inhibits Middle East respiratory syndrome-coronavirus replication in vitro. Viruses. 2018;10(6):283.
Ghasemnejad-Berenji M, Pashapour S. SARS-CoV-2 and the possible role of Raf/MEK/ERK pathway in viral survival: is this a potential therapeutic strategy for COVID-19? Pharmacology. 2021;106 (1-2):119-22.
Chen XY, Zhou J, Luo LP, Han B, Li F, Chen JY et al. Black rice anthocyanins suppress metastasis of breast cancer cells by targeting RAS/RAF/MAPK pathway. BioMed Res Int. 2015;2015:414250.
Magangana TP, Makunga NP, Fawole OA, Opara UL. Processing factors affecting the phytochemical and nutritional properties of pomegranate (Punica granatum L.) peel waste: a review. Molecules. 2020;25(20): 4690.
Babu PVA, Liu D. Green tea catechins and cardiovascular health: an update. Curr Med Chem. 2008;15(18):1840-50.
Zhang L, Deng M, Zhou S. Tetramethylpyrazine inhibits hypoxia-induced pulmonary vascular leakage in rats via the ROS-HIF-VEGF pathway. Pharmacology. 2011;87(5-6): 265-73.
Marchetti M. COVID-19-driven endothelial damage: complement, HIF-1, and ABL2 are potential pathways of damage and targets for cure. Ann Hematol. 2020;99(8):1701-7.
Zhou J, Liao W, Yang J, Ma K, Li X, Wang Y et al. FOXO3 induces FOXO1-dependent autophagy by activating the AKT1 signaling pathway. Autophagy. 2012;8(12):1712-23.
Shojaei S, Suresh M, Klionsky DJ, Labouta HI, Ghavami S. Autophagy and SARS-CoV-2 infection: Apossible smart targeting of the autophagy pathway. Virulence. 2020;11(1):805-10.
Farag RS, Abdel-Latif MS, Emam SS, Tawfeek SH. Phytochemical screening and polyphenol constituents of pomegranate peels and leave juices In p, editor.
-
Abstract View: 432 times
PDF Download: 65 times
