Molecular Mechanisms of Curcumin in COVID-19 Treatment and Prevention: A Global Health Perspective

Main Article Content

Nathan Roberts Robert E. Brown, MD L. Maximilian Buja, MD Priya Weerasinghe, MD, PhD

Abstract

Turmeric (Curcuma Longa) has a near 4000-year history of extensive medical use in South Asia. Its main physiologically active phytochemical is curcumin (diferuloylmethane), derived from the rhizome of turmeric. Curcumin is a hydrophobic polyphenol with a diketone moiety connecting two phenoxy rings. It is widely available, and exerts systemic and pleiotropic effects via several key mechanisms. Most famously, it is known to inhibit pro-inflammatory pathways such as PI3k/akt/NF-kB activation. It is also a potent antioxidant and free radical scavenger via a sequential proton loss electron transfer mechanism in ionizing solvents due to its extended conjugating ability across the entire molecule, and its ability to induce NRF-2. It has been implicated in the treatment of diseases ranging from asthma to various cancers, and is also a broad spectrum anti-microbial. COVID-19 is a novel beta-coronavirus that was declared a pandemic by the WHO in March, 2020. It is primarily a respiratory disorder, but it can spread hematogenously and effect many other organs such as the heart, nervous system, and kidneys. There is a significant intersection between the clinical manifestations of COVID-19 and curcumin’s therapeutic effects. In addition, curcumin has been shown to inhibit initial viral infectivity. Thus, there is potential for curcumin to safely both prevent and treat COVID-19 infection across the globe.

Keywords: COVID-19, Curcumin, Anti-viral, Anti-inflammatory, Anti-oxidant, Molecular mechanisms

Article Details

How to Cite
ROBERTS, Nathan et al. Molecular Mechanisms of Curcumin in COVID-19 Treatment and Prevention: A Global Health Perspective. Medical Research Archives, [S.l.], v. 8, n. 10, nov. 2020. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2248>. Date accessed: 08 dec. 2024. doi: https://doi.org/10.18103/mra.v8i10.2248.
Section
Research Articles

References

1. Curcumin: the Indian solid gold. Life Extension. Published online August 2012. Accessed June 3, 2020. https://link.gale.com/apps/doc/A300995712/HRCA?u=txshracd2509&sid=HRCA&xid=0cb19d56
2. Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine. CRC Press; 2011:310. doi:10.1201/b10787-19
3. Miyakoshi M, Yamaguchi Y, Takagaki R, et al. Hepatoprotective effect of sesquiterpenes in turmeric. BioFactors. 2004;21(1-4):167-170. doi:10.1002/biof.552210134
4. Litwinienko G, Ingold KU. Abnormal Solvent Effects on Hydrogen Atom Abstraction. 2. Resolution of the Curcumin Antioxidant Controversy. The Role of Sequential Proton Loss Electron Transfer. J Org Chem. 2004;69(18):5888-5896. doi:10.1021/jo049254j
5. Aggarwal BB, Ichikawa H, Garodia P, et al. From traditional Ayurvedic medicine to modern medicine: identification of therapeutic targets for suppression of inflammation and cancer. Expert Opinion on Therapeutic Targets. 2006;10(1):87-118. doi:10.1517/14728222.10.1.87
6. Yuan J, Liu R, Ma Y, Zhang Z, Xie Z. Curcumin Attenuates Airway Inflammation and Airway Remolding by Inhibiting NF-κB Signaling and COX-2 in Cigarette Smoke-Induced COPD Mice. Inflammation. 2018;41(5):1804-1814. doi:10.1007/s10753-018-0823-6
7. Kant V, Gopal A, Pathak NN, Kumar P, Tandan SK, Kumar D. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats. Int Immunopharmacol. 2014;20(2):322-330. doi:10.1016/j.intimp.2014.03.009
8. Zorofchian Moghadamtousi S, Abdul Kadir H, Hassandarvish P, Tajik H, Abubakar S, Zandi K. A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin. BioMed Research International. 2014;2014:1-12. doi:10.1155/2014/186864
9. Roman-Blas JA, Stokes DG, Jimenez SA. Modulation of TGF-β signaling by proinflammatory cytokines in articular chondrocytes. Osteoarthritis and Cartilage. 2007;15(12):1367-1377. doi:10.1016/j.joca.2007.04.011
10. Kang B-Y, Khan JA, Ryu S, Shekhar R, Seung K-B, Mehta JL. Curcumin Reduces Angiotensin II–mediated Cardiomyocyte Growth via LOX-1 Inhibition: Journal of Cardiovascular Pharmacology. 2010;55(4):417-424. doi:10.1097/FJC.0b013e3181ca4ba1
11. Xia X, Cheng G, Pan Y, Xia ZH, Kong LD. Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa L. in the mouse forced swimming test. Journal of Ethnopharmacology. 2007;110(2):356-363. doi:10.1016/j.jep.2006.09.042
12. Mohanty I, Arya DS, Gupta SK. Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in experimentally induced myocardial ischemic-reperfusion injury. Mohanty I, ed. BMC complementary and alternative medicine. 2006;6:3-3.
13. Zahid Ashraf M, Hussain ME, Fahim M. Antiatherosclerotic effects of dietary supplementations of garlic and turmeric: Restoration of endothelial function in rats. Life Sciences. 2005;77(8):837-857. doi:10.1016/j.lfs.2004.11.039
14. Bundy R, Walker AF, Middleton RW, Booth J. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study. Bundy R, ed. Journal of alternative and complementary medicine (New York, NY). 2004;10(6):1015-1018. doi:10.1089/acm.2004.10.1015
15. Kulkarni SK, Dhir A. An overview of curcumin in neurological disorders. Indian J Pharm Sci. 2010;72(2):149-154. doi:10.4103/0250-474X.65012
16. Montalvan V, Lee J, Bueso T, De Toledo J, Rivas K. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clinical Neurology and Neurosurgery. 2020;194:105921. doi:10.1016/j.clineuro.2020.105921
17. Guo Y-R, Cao Q-D, Hong Z-S, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Military Med Res. 2020;7(1):11. doi:10.1186/s40779-020-00240-0
18. Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z. Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19). J GEN INTERN MED. 2020;35(5):1545-1549. doi:10.1007/s11606-020-05762-w
19. Mathew D, Hsu W-L. Antiviral potential of curcumin. Journal of Functional Foods. 2018;40:692-699. doi:10.1016/j.jff.2017.12.017
20. Chen T-Y, Chen D-Y, Wen H-W, et al. Inhibition of Enveloped Viruses Infectivity by Curcumin. Harrich D, ed. PLoS ONE. 2013;8(5):e62482. doi:10.1371/journal.pone.0062482
21. Utomo RY, Ikawati M, Meiyanto E. Revealing the Potency of Citrus and Galangal Constituents to Halt SARS-CoV-2 Infection. MEDICINE & PHARMACOLOGY; 2020. doi:10.20944/preprints202003.0214.v1
22. Khaerunnisa S, Kurniawan H, Awaluddin R, Suhartati S, Soetjipto S. Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study. MEDICINE & PHARMACOLOGY; 2020. doi:10.20944/preprints202003.0226.v1
23. Avasarala S, Zhang F, Liu G, Wang R, London SD, London L. Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome. Reddy R, ed. PLoS ONE. 2013;8(2):e57285. doi:10.1371/journal.pone.0057285
24. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet. 2020;395(10236):1569-1578. doi:10.1016/S0140-6736(20)31022-9
25. Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-1799. doi:10.1056/NEJMoa2001282
26. Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. Published online March 20, 2020:105949. doi:10.1016/j.ijantimicag.2020.105949
27. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. (Abstracts). Alternative Medicine Review. 2002;7(1):82.
28. Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol. 2020;92(4):418-423. doi:10.1002/jmv.25681
29. Xu Y, Li X, Zhu B, et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020;26(4):502-505. doi:10.1038/s41591-020-0817-4
30. Ashour HM, Elkhatib WF, Rahman MdM, Elshabrawy HA. Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks. Pathogens. 2020;9(3):186. doi:10.3390/pathogens9030186
31. Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020;181(2):281-292.e6. doi:10.1016/j.cell.2020.02.058
32. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-637. doi:10.1002/path.1570
33. Kabbani N, Olds JL. Does COVID19 Infect the Brain? If So, Smokers Might Be at a Higher Risk. Mol Pharmacol. 2020;97(5):351-353. doi:10.1124/molpharm.120.000014
34. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239. doi:10.1001/jama.2020.2648
35. Batlle D, Soler MJ, Sparks MA, et al. Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct Pathophysiology. JASN. 2020;31(7):1380-1383. doi:10.1681/ASN.2020040419
36. Ibáñez S, Martínez O, Valenzuela F, Silva F, Valenzuela O. Hydroxychloroquine and chloroquine in COVID-19: should they be used as standard therapy? Clin Rheumatol. 2020;39(8):2461-2465. doi:10.1007/s10067-020-05202-4
37. Alsop RJ, Dhaliwal A, Rheinstädter MC. Curcumin Protects Membranes through a Carpet or Insertion Model Depending on Hydration. Langmuir. 2017;33(34):8516-8524. doi:10.1021/acs.langmuir.7b01562
38. Hung W-C, Chen F-Y, Lee C-C, Sun Y, Lee M-T, Huang HW. Membrane-Thinning Effect of Curcumin. Biophysical Journal. 2008;94(11):4331-4338. doi:10.1529/biophysj.107.126888
39. Ingólfsson HI, Thakur P, Herold KF, et al. Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function. ACS Chem Biol. 2014;9(8):1788-1798. doi:10.1021/cb500086e
40. Mohanty C, Das M, Sahoo SK. Sustained Wound Healing Activity of Curcumin Loaded Oleic Acid Based Polymeric Bandage in a Rat Model. Mol Pharmaceutics. 2012;9(10):2801-2811. doi:10.1021/mp300075u
41. Ma Q-L, Yang F, Rosario ER, et al. Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci. 2009;29(28):9078-9089. doi:10.1523/JNEUROSCI.1071-09.2009
42. Jung Y, Xu W, Kim H, Ha N, Neckers L. Curcumin-induced degradation of ErbB2: A role for the E3 ubiquitin ligase CHIP and the Michael reaction acceptor activity of curcumin. BBA - Molecular Cell Research. 2007;1773(3):383-390. doi:10.1016/j.bbamcr.2006.11.004
43. Mohanty C, Sahoo SK. The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. Biomaterials. 2010;31(25):6597-6611. doi:10.1016/j.biomaterials.2010.04.062
44. Chen A, Xu J. Activation of PPARγ by curcumin inhibits Moser cell growth and mediates suppression of gene expression of cyclin D1 and EGFR. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2005;288(3):G447-G456. doi:10.1152/ajpgi.00209.2004
45. Eggler AL, Gay KA, Mesecar AD. Molecular mechanisms of natural products in chemoprevention: Induction of cytoprotective enzymes by Nrf2. Mol Nutr Food Res. Published online April 24, 2008. doi:10.1002/mnfr.200700249
46. He Q, Liu J, Liang J, et al. Towards Improvements for Penetrating the Blood-Brain Barrier-Recent Progress from a Material and Pharmaceutical Perspective. Cells. 2018;7(4). doi:10.3390/cells7040024
47. Tilak JC, Banerjee M, Mohan H, Devasagayam TPA. Antioxidant availability of turmeric in relation to its medicinal and culinary uses. Phytother Res. 2004;18(10):798-804. doi:10.1002/ptr.1553
48. Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2. doi:10.1038/sigtrans.2017.23
49. Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB. Curcumin (Diferuloylmethane) Down-Regulates Expression of Cell Proliferation and Antiapoptotic and Metastatic Gene Products through Suppression of IκBα Kinase and Akt Activation. Mol Pharmacol. 2006;69(1):195-206. doi:10.1124/mol.105.017400
50. Jagetia GC, Aggarwal BB. “Spicing Up” of the Immune System by Curcumin. J Clin Immunol. 2007;27(1):19-35. doi:10.1007/s10875-006-9066-7
51. Ranjan D, Chen C, Johnston TD, Jeon H, Nagabhushan M. Curcumin inhibits mitogen stimulated lymphocyte proliferation, NFκB activation, and IL-2 signaling. Journal of Surgical Research. 2004;121(2):171-177. doi:10.1016/j.jss.2004.04.004
52. Li X, Liu X. Effect of curcumin on immune function of mice. J Huazhong Univ Sci Technol Med Sci. 2005;25(2):137-140. doi:10.1007/BF02873559
53. Ranjan D, Siquijor A, Johnston TD, Wu G, Nagabhuskahn M. The effect of curcumin on human B-cell immortalization by Epstein-Barr virus. Am Surg. 1998;64(1):47-51; discussion 51-52.
54. Yang Z-S, Peng Z-H, Li X-L, Song J-W, Ren J-W. Effect of curcumin on IL-17-induced nitric oxide production and expression of iNOS in human keratinocytes. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology. 2011;27(9):959.
55. Ravindran J, Prasad S, Aggarwal BB. Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively? AAPS J. 2009;11(3):495-510. doi:10.1208/s12248-009-9128-x
56. Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini KI. Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochimica et Biophysica Acta (BBA) - General Subjects. 2008;1780(4):673-679. doi:10.1016/j.bbagen.2007.11.016
57. Ghoneim AI. Effects of curcumin on ethanol-induced hepatocyte necrosis and apoptosis: implication of lipid peroxidation and cytochrome c. Naunyn-Schmied Arch Pharmacol. 2009;379(1):47-60. doi:10.1007/s00210-008-0335-2
58. Moghtaderi H, Sepehri H, Delphi L, Attari F. Gallic acid and curcumin induce cytotoxicity and apoptosis in human breast cancer cell MDA-MB-231. Bioimpacts. 2018;8(3):185-194. doi:10.15171/bi.2018.21
59. Yao Y, Wang W, Li M, et al. Curcumin Exerts its Anti-hypertensive Effect by Down-regulating the AT1 Receptor in Vascular Smooth Muscle Cells. Sci Rep. 2016;6:25579. doi:10.1038/srep25579
60. Paravicini T, Touyz R. Redox signaling in hypertension. Cardiovascular Research. 2006;71(2):247-258. doi:10.1016/j.cardiores.2006.05.001
61. Hao Q, Chen X, Wang X, Dong B, Yang C. Curcumin Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm by Inhibition of Inflammatory Response and ERK Signaling Pathways. Evidence-Based Complementary and Alternative Medicine. 2014;2014:1-10. doi:10.1155/2014/270930
62. Zhao Z-Q, Pang X-F, Zhang L-H, et al. Attenuation of myocardial fibrosis with curcumin is mediated by modulating expression of angiotensin II AT1/AT2 receptors and ACE2 in rats. DDDT. Published online November 2015:6043. doi:10.2147/DDDT.S95333
63. Jones ES, Vinh A, McCarthy CA, Gaspari TA, Widdop RE. AT2 receptors: Functional relevance in cardiovascular disease. Pharmacology & Therapeutics. 2008;120(3):292-316. doi:10.1016/j.pharmthera.2008.08.009
64. Einbond LS, Manservisi F, Wu H, et al. A transcriptomic analysis of turmeric: Curcumin represses the expression of cholesterol biosynthetic genes and synergizes with simvastatin. Pharmacological Research. 2018;132:176-187. doi:10.1016/j.phrs.2018.01.023
65. Wang Z, Zhang Q, Yuan L, et al. The effects of curcumin on depressive-like behavior in mice after lipopolysaccharide administration. Behavioural Brain Research. 2014;274:282-290. doi:10.1016/j.bbr.2014.08.018
66. Xu Y, Ku B-S, Yao H-Y, et al. The effects of curcumin on depressive-like behaviors in mice. European Journal of Pharmacology. 2005;518(1):40-46. doi:10.1016/j.ejphar.2005.06.002
67. Ak T, Gülçin İ. Antioxidant and radical scavenging properties of curcumin. Chemico-Biological Interactions. 2008;174(1):27-37. doi:10.1016/j.cbi.2008.05.003
68. Singh R, Sharma P. Hepatoprotective Effect of Curcumin on Lindane-induced Oxidative Stress in Male Wistar Rats. Toxicol Int. 2011;18(2):124-129. doi:10.4103/0971-6580.84264
69. Salama SM, Abdulla MA, AlRashdi AS, Ismail S, Alkiyumi SS, Golbabapour S. Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats. BMC Complement Altern Med. 2013;13(1):56. doi:10.1186/1472-6882-13-56
70. Wang M-E, Chen Y-C, Chen I-S, Hsieh S-C, Chen S-S, Chiu C-H. Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes. The Journal of Nutritional Biochemistry. 2012;23(10):1352-1366. doi:10.1016/j.jnutbio.2011.08.004
71. Trujillo J, Chirino YI, Molina-Jijón E, Andérica-Romero AC, Tapia E, Pedraza-Chaverrí J. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol. 2013;1:448-456. doi:10.1016/j.redox.2013.09.003
72. Kuhad A, Pilkhwal S, Sharma S, Tirkey N, Chopra K. Effect of Curcumin on Inflammation and Oxidative Stress in Cisplatin-Induced Experimental Nephrotoxicity. J Agric Food Chem. 2007;55(25):10150-10155. doi:10.1021/jf0723965
73. Xu X, Cai Y, Yu Y. Effects of a novel curcumin derivative on the functions of kidney in streptozotocin-induced type 2 diabetic rats. Inflammopharmacology. 2018;26(5):1257-1264. doi:10.1007/s10787-018-0449-1
74. Hong J. Modulation of arachidonic acid metabolism by curcumin and related -diketone derivatives: effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipoxygenase. Carcinogenesis. 2004;25(9):1671-1679. doi:10.1093/carcin/bgh165
75. Skrzypczak-Jankun E, Zhou K, Mccabe NP, Selman SH, Jankun J. Structure of curcumin in complex with lipoxygenase and its significance in cancer. Skrzypczak-Jankun E, ed. International journal of molecular medicine. 2003;12(1):17-24.
76. Niamsa N, Sittiwet C. Antimicrobial Activity of Curcuma longa Aqueous Extract. J of Pharmacology and Toxicology. 2009;4(4):173-177. doi:10.3923/jpt.2009.173.177
77. O’Mahony R, Al-Khtheeri H, Weerasekera D, et al. Bactericidal and anti-adhesive properties of culinary and medicinal plants against Helicobacter pylori. O’Mahony R, ed. World journal of gastroenterology. 2005;11(47):7499-7507. doi:10.3748/wjg.v11.i47.7499
78. Kaur S, Modi NH, Panda D, Roy N. Probing the binding site of curcumin in Escherichia coli and Bacillus subtilis FtsZ--a structural insight to unveil antibacterial activity of curcumin. Eur J Med Chem. 2010;45(9):4209-4214. doi:10.1016/j.ejmech.2010.06.015
79. Dairaku I, Han Y, Yanaka N, Kato N. Inhibitory Effect of Curcumin on IMP Dehydrogenase, the Target for Anticancer and Antiviral Chemotherapy Agents. Bioscience, Biotechnology, and Biochemistry. 2010;74(1):185-187. doi:10.1271/bbb.90568
80. Ludwig S, Planz O. Influenza viruses and the NF-κB signaling pathway – towards a novel concept of antiviral therapy. Biological Chemistry. 2008;389(10). doi:10.1515/BC.2008.148
81. Si X, Wang Y, Wong J, Zhang J, McManus BM, Luo H. Dysregulation of the Ubiquitin-Proteasome System by Curcumin Suppresses Coxsackievirus B3 Replication. JVI. 2007;81(7):3142-3150. doi:10.1128/JVI.02028-06
82. Ahmed J, Tan Y, Ambegaokar S. Effects of Curcumin on Vesicular Stomatitis Virus (VSV) Infection and Dicer-1 Expression. The FASEB Journal. 2017;31(S1):622.11-622.11. doi:10.1096/fasebj.31.1_supplement.622.11
83. Vajragupta O, Boonchoong P, Morris GM, Olson AJ. Active site binding modes of curcumin in HIV-1 protease and integrase. Bioorganic & Medicinal Chemistry Letters. 2005;15(14):3364-3368. doi:10.1016/j.bmcl.2005.05.032
84. Narayan V, Ravindra KC, Chiaro C, et al. Celastrol Inhibits Tat-Mediated Human Immunodeficiency Virus (HIV) Transcription and Replication. Journal of Molecular Biology. 2011;410(5):972-983. doi:10.1016/j.jmb.2011.04.013
85. Shahabi nezhad F, Mosaddeghi P, Negahdaripour M, et al. Therapeutic Approaches for COVID-19 Based on the Dynamics of Interferon-Mediated Immune Responses. MEDICINE & PHARMACOLOGY; 2020. doi:10.20944/preprints202003.0206.v2
86. Ting D, Dong N, Fang L, et al. Multisite Inhibitors for Enteric Coronavirus: Antiviral Cationic Carbon Dots Based on Curcumin. ACS Appl Nano Mater. 2018;1(10):5451-5459. doi:10.1021/acsanm.8b00779
87. Yan S-F, Mackman N, Kisiel W, Stern DM, Pinsky DJ. Hypoxia/Hypoxemia-Induced Activation of the Procoagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis. Arterioscler Thromb Vasc Biol. 1999;19(9):2029-2035. doi:10.1161/01.ATV.19.9.2029
88. Kim D-C, Ku S-K, Bae J-S. Anticoagulant activities of curcumin and its derivative. BMB Rep. 2012;45(4):221-226. doi:10.5483/bmbrep.2012.45.4.221
89. Zahedipour F, Hosseini SA, Sathyapalan T, et al. Potential effects of curcumin in the treatment of COVID ‐19 infection. Phytotherapy Research. Published online June 23, 2020:ptr.6738. doi:10.1002/ptr.6738
90. Gupta H, Gupta M, Bhargava S. Potential use of turmeric in COVID‐19. Clin Exp Dermatol. Published online July 27, 2020:ced.14357. doi:10.1111/ced.14357
91. Liu Z, Ying Y. The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and Its Potential Use in the Associated Severe Pneumonia. Front Cell Dev Biol. 2020;8:479. doi:10.3389/fcell.2020.00479
92. Rocha FAC, Assis MR. Curcumin as a potential treatment for COVID ‐19. Phytotherapy Research. Published online June 9, 2020:ptr.6745. doi:10.1002/ptr.6745
93. Maurya VK, Kumar S, Prasad AK, Bhatt MLB, Saxena SK. Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor. Virusdisease. 2020;31(2):179-193. doi:10.1007/s13337-020-00598-8