Curcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanisms

Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound agains...

Full description

Autores:
Marín Palma, Damariz
Tabares Guevara, Jorge
Zapata Cardona, María Isabel
Flórez Álvarez, Lizdany
Yepes, Lina M.
Rugeles López, María Teresa
Zapata Builes, Wildeman
Hernández López, Juan Carlos
Taborda, Natalia Andrea
Tipo de recurso:
Article of investigation
Fecha de publicación:
2021
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/44426
Acceso en línea:
https://hdl.handle.net/20.500.12494/44426
Palabra clave:
Curcumin
Antiviral
COVID-19
SARS-CoV-2
Immune response
Inflammation
D614G strain
Delta variant
Rights
openAccess
License
Atribución
id COOPER2_1b67e60a923f851e842152e655fe546c
oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/44426
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv Curcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanisms
title Curcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanisms
spellingShingle Curcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanisms
Curcumin
Antiviral
COVID-19
SARS-CoV-2
Immune response
Inflammation
D614G strain
Delta variant
title_short Curcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanisms
title_full Curcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanisms
title_fullStr Curcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanisms
title_full_unstemmed Curcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanisms
title_sort Curcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanisms
dc.creator.fl_str_mv Marín Palma, Damariz
Tabares Guevara, Jorge
Zapata Cardona, María Isabel
Flórez Álvarez, Lizdany
Yepes, Lina M.
Rugeles López, María Teresa
Zapata Builes, Wildeman
Hernández López, Juan Carlos
Taborda, Natalia Andrea
dc.contributor.author.none.fl_str_mv Marín Palma, Damariz
Tabares Guevara, Jorge
Zapata Cardona, María Isabel
Flórez Álvarez, Lizdany
Yepes, Lina M.
Rugeles López, María Teresa
Zapata Builes, Wildeman
Hernández López, Juan Carlos
Taborda, Natalia Andrea
dc.subject.spa.fl_str_mv Curcumin
Antiviral
COVID-19
SARS-CoV-2
Immune response
Inflammation
D614G strain
Delta variant
topic Curcumin
Antiviral
COVID-19
SARS-CoV-2
Immune response
Inflammation
D614G strain
Delta variant
description Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound against SARS-CoV-2 was evaluated using four treatment strategies (i. pre–post infection treatment, ii. co-treatment, iii. pre-infection, and iv. post-infection). The D614G strain and Delta variant of SARS-CoV-2 were used, and the viral titer was quantified by plaque assay. The anti-inflammatory effect was evaluated in peripheral blood mononuclear cells (PBMCs) using qPCR and ELISA. By pre–post infection treatment, Curcumin (10 µg/mL) exhibited antiviral effect of 99% and 99.8% against DG614 strain and Delta variant, respectively. Curcumin also inhibited D614G strain by pre-infection and post-infection treatment. In addition, curcumin showed a virucidal effect against D614G strain and Delta variant. Finally, the pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) released by PBMCs triggered by SARS-CoV-2 were decreased after treatment with curcumin. Our results suggest that curcumin affects the SARS-CoV-2 replicative cycle and exhibits virucidal effect with a variant/strain independent antiviral effect and immune-modulatory properties. This is the first study that showed a combined (antiviral/anti-inflammatory) effect of curcumin during SARS-CoV-2 infection. However, additional studies are required to define its use as a treatment for the COVID-19.
publishDate 2021
dc.date.issued.none.fl_str_mv 2021-11-16
dc.date.accessioned.none.fl_str_mv 2022-03-16T19:46:20Z
dc.date.available.none.fl_str_mv 2022-03-16T19:46:20Z
dc.type.none.fl_str_mv Artículos Científicos
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coarversion.none.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.uri.spa.fl_str_mv 10.3390/molecules26226900
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/44426
dc.identifier.bibliographicCitation.spa.fl_str_mv Marín-Palma D, Tabares-Guevara JH, Zapata-Cardona MI, Flórez-Álvarez L, Yepes LM, Rugeles MT, Zapata-Builes W, Hernandez JC, Taborda NA. (2021) Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms. Molecules. 2021 Nov 16;26(22):6900. doi: 10.3390/molecules26226900. http://hdl.handle.net/20.500.12494/44426
identifier_str_mv 10.3390/molecules26226900
Marín-Palma D, Tabares-Guevara JH, Zapata-Cardona MI, Flórez-Álvarez L, Yepes LM, Rugeles MT, Zapata-Builes W, Hernandez JC, Taborda NA. (2021) Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms. Molecules. 2021 Nov 16;26(22):6900. doi: 10.3390/molecules26226900. http://hdl.handle.net/20.500.12494/44426
url https://hdl.handle.net/20.500.12494/44426
dc.relation.isversionof.spa.fl_str_mv https://www.mdpi.com/1420-3049/26/22/6900
dc.relation.ispartofjournal.spa.fl_str_mv Molecules
dc.relation.references.spa.fl_str_mv Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; et al. Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, 588
Woo, P.C.; Lau, S.K.; Huang, Y.; Yuen, K.Y. Coronavirus diversity, phylogeny and interspecies jumping. Exp. Biol. Med. (Maywood) 2009, 234, 1117–1127
Su, S.; Wong, G.; Shi, W.; Liu, J.; Lai, A.C.K.; Zhou, J.; Liu, W.; Bi, Y.; Gao, G.F. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol. 2016, 24, 490–502
Forni, D.; Cagliani, R.; Clerici, M.; Sironi, M. Molecular Evolution of Human Coronavirus Genomes. Trends Microbiol. 2017, 25, 35–48.
Malik, Y.A. Properties of Coronavirus and SARS-CoV-2. Malays. J. Pathol. 2020, 42, 3–11
Sun, J.; He, W.T.; Wang, L.; Lai, A.; Ji, X.; Zhai, X.; Li, G.; Suchard, M.A.; Tian, J.; Zhou, J.; et al. COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives. Trends Mol. Med. 2020, 26, 483–495
Du, L.; He, Y.; Zhou, Y.; Liu, S.; Zheng, B.J.; Jiang, S. The spike protein of SARS-CoV—A target for vaccine and therapeutic development. Nat. Rev. Microbiol. 2009, 7, 226–236.
Walls, A.C.; Park, Y.J.; Tortorici, M.A.; Wall, A.; McGuire, A.T.; Veesler, D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020, 183, 1735
Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; et al. Genomic characterisation and epidemiology of 2019 novel coronavirus:Implications for virus origins and receptor binding. Lancet 2020, 395, 565–574
Ghanbari, R.; Teimoori, A.; Sadeghi, A.; Mohamadkhani, A.; Rezasoltani, S.; Asadi, E.; Jouyban, A.; Sumner, S.C. Existing antiviral options against SARS-CoV-2 replication in COVID-19 patients. Future Microbiol. 2020, 15, 1747–1758.
Paces, J.; Strizova, Z.; Smrz, D.; Cerny, J. COVID-19 and the immune system. Physiol. Res. 2020, 69, 379–388
Aguilar-Jiménez, W.; Flórez-Álvarez, L.; Rincón, D.S.; Marín-Palma, D.; Sánchez-Martínez, A.; Martínez, J.; Zapata, M.I.; Loaiza, J.D.; Cárdenas, C.; Guzmán, F.; et al. Caracterización inmunológica de un grupo familiar colombiano con infección por SARS-CoV-2. Biomedica 2021, 41, 86–102
Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506.
Xiong, Y.; Liu, Y.; Cao, L.; Wang, D.; Guo, M.; Jiang, A.; Guo, D.; Hu, W.; Yang, J.; Tang, Z.; et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg. Microbes Infect 2020, 9, 761–770
Mani, J.S.; Johnson, J.B.; Steel, J.C.; Broszczak, D.A.; Neilsen, P.M.; Walsh, K.B.; Naiker, M. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020, 284, 197989
Yepes-Perez, A.F.; Herrera-Calderon, O.; Oliveros, C.A.; Florez-Alvarez, L.; Zapata-Cardona, M.I.; Yepes, L.; Aguilar-Jimenez, W.; Rugeles, M.T.; Zapata, W. The Hydroalcoholic Extract of Uncaria tomentosa (Cat’s Claw) Inhibits the Infection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) In Vitro. Evid. Based Complement. Altern. Med. 2021, 2021, 6679761.
Moghadamtousi, S.Z.; Kadir, H.A.; Hassandarvish, P.; Tajik, H.; Abubakar, S.; Zandi, K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed. Res. Int. 2014, 2014, 186864.
Gupta, H.; Gupta, M.; Bhargava, S. Potential use of turmeric in COVID-19. Clin. Exp. Derm. 2020, 45, 902–903. [CrossRef] 19. Sahebkar, A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res. 2014, 28, 633–642
Sahebkar, A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res. 2014, 28, 633–642.
Ranjan, D.; Chen, C.; Johnston, T.D.; Jeon, H.; Nagabhushan, M. Curcumin inhibits mitogen stimulated lymphocyte proliferation, NFkappaB activation, and IL-2 signaling. J. Surg. Res. 2004, 121, 171–177.
Gong, Z.; Zhou, J.; Li, H.; Gao, Y.; Xu, C.; Zhao, S.; Chen, Y.; Cai, W.; Wu, J. Curcumin suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock. Mol. Nutr. Food Res. 2015, 59, 2132–2142.
Yin, H.; Guo, Q.; Li, X.; Tang, T.; Li, C.; Wang, H.; Sun, Y.; Feng, Q.; Ma, C.; Gao, C.; et al. Curcumin Suppresses IL-1beta Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome. J. Immunol. 2018, 200, 2835–2846.
Balasubramanian, A.; Pilankatta, R.; Teramoto, T.; Sajith, A.M.; Nwulia, E.; Kulkarni, A.; Padmanabhan, R. Inhibition of dengue virus by curcuminoids. Antivir. Res. 2019, 162, 71–78.
Mounce, B.C.; Cesaro, T.; Carrau, L.; Vallet, T.; Vignuzzi, M. Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding. Antivir. Res. 2017, 142, 148–157.
Richart, S.M.; Li, Y.L.; Mizushina, Y.; Chang, Y.Y.; Chung, T.Y.; Chen, G.H.; Tzen, J.T.; Shia, K.S.; Hsu, W.L. Synergic effect of curcumin and its structural analogue (Monoacetylcurcumin) on anti-influenza virus infection. J. Food Drug Anal. 2018, 26, 1015–1023.
Mazumder, A.; Raghavan, K.; Weinstein, J.; Kohn, K.W.; Pommier, Y. Inhibition of human immunodeficiency virus type-1 integrase by curcumin. Biochem. Pharm. 1995, 49, 1165–1170.
Ali, A.; Banerjea, A.C. Curcumin inhibits HIV-1 by promoting Tat protein degradation. Sci. Rep. 2016, 6, 27539
Jena, A.B.; Kanungo, N.; Nayak, V.; Chainy, G.B.N.; Dandapat, J. Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane:Insights from computational studies. Sci. Rep. 2021, 11, 2043.
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Kruger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020, 181, 271–280
Padmanabhan, P.; Desikan, R.; Dixit, N.M. Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARSCoV-2 infection. PLoS Comput. Biol. 2020, 16, e1008461.
Praditya, D.; Kirchhoff, L.; Bruning, J.; Rachmawati, H.; Steinmann, J.; Steinmann, E. Anti-infective Properties of the Golden Spice Curcumin. Front Microbiol. 2019, 10, 912
Korber, B.; Fischer, W.M.; Gnanakaran, S.; Yoon, H.; Theiler, J.; Abfalterer, W.; Hengartner, N.; Giorgi, E.E.; Bhattacharya, T.; Foley, B.; et al. Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell 2020, 182, 812–827.e819
Khateeb, J.; Li, Y.; Zhang, H. Emerging SARS-CoV-2 variants of concern and potential intervention approaches. Crit. Care 2021, 25, 244.
Trujillo-Correa, A.I.; Quintero-Gil, D.C.; Diaz-Castillo, F.; Quiñones, W.; Robledo, S.M.; Martinez-Gutierrez, M. In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting. BMC Complement. Altern. Med. 2019, 19, 298.
Chen, D.-Y.; Shien, J.-H.; Tiley, L.; Chiou, S.-S.; Wang, S.-Y.; Chang, T.-J.; Lee, Y.-J.; Chan, K.-W.; Hsu, W.-L. Curcumin inhibits influenza virus infection and haemagglutination activity. Food Chem. 2010, 119, 1346–1351. [
Chen, T.Y.; Chen, D.Y.; Wen, H.W.; Ou, J.L.; Chiou, S.S.; Chen, J.M.; Wong, M.L.; Hsu, W.L. Inhibition of enveloped viruses infectivity by curcumin. PLoS ONE 2013, 8, e62482.
Zandi, K.; Teoh, B.T.; Sam, S.S.; Wong, P.F.; Mustafa, M.R.; Abubakar, S. Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol. J. 2011, 8, 560
Kandeel, M.; Al-Nazawi, M. Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease. Life Sci. 2020, 251, 117627.
Katta, S.; Srivastava, A.; Thangapazham, R.L.; Rosner, I.L.; Cullen, J.; Li, H.; Sharad, S. Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells. Int. J. Mol. Sci. 2019, 20, 4891. [
Yang, X.X.; Li, C.M.; Huang, C.Z. Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection. Nanoscale 2016, 8, 3040–3048.
Wu, J.; Hou, W.; Cao, B.; Zuo, T.; Xue, C.; Leung, A.W.; Xu, C.; Tang, Q.J. Virucidal efficacy of treatment with photodynamically activated curcumin on murine norovirus bio-accumulated in oysters. Photodiagnosis. Photodyn. 2015, 12, 385–392.
Tang, T.; Bidon, M.; Jaimes, J.A.; Whittaker, G.R.; Daniel, S. Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antivir. Res. 2020, 178, 104792
Koch, J.; Uckeley, Z.M.; Doldan, P.; Stanifer, M.; Boulant, S.; Lozach, P.-Y. Host Cell Proteases Drive Early or Late SARS-CoV-2 Penetration. bioRxiv 2020. [
Nagahama, K.; Utsumi, T.; Kumano, T.; Maekawa, S.; Oyama, N.; Kawakami, J. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency. Sci. Rep. 2016, 6, 30962
Wen, C.C.; Kuo, Y.H.; Jan, J.T.; Liang, P.H.; Wang, S.Y.; Liu, H.G.; Lee, C.K.; Chang, S.T.; Kuo, C.J.; Lee, S.S.; et al. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. J. Med. Chem. 2007, 50, 4087–4095.
Obata, K.; Kojima, T.; Masaki, T.; Okabayashi, T.; Yokota, S.; Hirakawa, S.; Nomura, K.; Takasawa, A.; Murata, M.; Tanaka, S.; et al. Curcumin prevents replication of respiratory syncytial virus and the epithelial responses to it in human nasal epithelial cells. PLoS ONE 2013, 8, e70225.
Mathew, D.; Hsu, W.-L. Antiviral potential of curcumin. J. Funct. Foods 2018, 40, 692–699. [
Khaerunnisa, S.K.H.; Awaluddin, R.; Suhartati, S.; Soetjipto, S. Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study. Preprints 2020.
Kumar, M.; Sodhi, K.K.; Singh, D.K. Addressing the potential role of curcumin in the prevention of COVID-19 by targeting the Nsp9 replicase protein through molecular docking. Arch. Microbiol. 2021, 203, 1691–1696
Planas, D.; Veyer, D.; Baidaliuk, A.; Staropoli, I.; Guivel-Benhassine, F.; Rajah, M.M.; Planchais, C.; Porrot, F.; Robillard, N.; Puech, J.; et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 2021, 596, 276–280.
Du, T.; Nan, Y.; Xiao, S.; Zhao, Q.; Zhou, E.M. Antiviral Strategies against PRRSV Infection. Trends Microbiol. 2017, 25, 968–979.
Lopez Bernal, J.; Andrews, N.; Gower, C.; Gallagher, E.; Simmons, R.; Thelwall, S.; Stowe, J.; Tessier, E.; Groves, N.; Dabrera, G.; et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N. Engl. J. Med. 2021, 385, 585–594.
Blanco-Melo, D.; Nilsson-Payant, B.E.; Liu, W.C.; Uhl, S.; Hoagland, D.; Moller, R.; Jordan, T.X.; Oishi, K.; Panis, M.; Sachs, D.; et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell 2020, 181, 1036–1045.
Hirano, T.; Murakami, M. COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome. Immunity 2020, 52, 731–733
Vardhana, S.A.; Wolchok, J.D. The many faces of the anti-COVID immune response. J. Exp. Med. 2020, 217
Valizadeh, H.; Abdolmohammadi-Vahid, S.; Danshina, S.; Ziya Gencer, M.; Ammari, A.; Sadeghi, A.; Roshangar, L.; Aslani, S.; Esmaeilzadeh, A.; Ghaebi, M.; et al. Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients. Int. Immunol. 2020, 89, 107088
Haneklaus, M.; O’Neill, L.A. NLRP3 at the interface of metabolism and inflammation. Immunol. Rev. 2015, 265, 53–62.
Zhang, S.; Zou, J.; Li, P.; Zheng, X.; Feng, D. Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by Inhibiting Toll-like Receptor 4 Expression. J. Agric. Food Chem. 2018, 66, 449–456
Xu, Y.; Liu, L. Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF-kappaB signaling pathway. Influenza Other Respir. Viruses 2017, 11, 457–463
Hasanzadeh, S.; Read, M.I.; Bland, A.R.; Majeed, M.; Jamialahmadi, T.; Sahebkar, A. Curcumin: An inflammasome silencer. Pharm. Res. 2020, 159, 104921
Dai, Q.; Zhou, D.; Xu, L.; Song, X. Curcumin alleviates rheumatoid arthritis-induced inflammation and synovial hyperplasia by targeting mTOR pathway in rats. Drug Des. Devel. 2018, 12, 4095–4105
Hasan, S.T.; Zingg, J.M.; Kwan, P.; Noble, T.; Smith, D.; Meydani, M. Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice. Atherosclerosis 2014, 232, 40–51.
Lim, G.P.; Chu, T.; Yang, F.; Beech, W.; Frautschy, S.A.; Cole, G.M. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Neurosci. 2001, 21, 8370–8377
Mohajeri, M.; Sadeghizadeh, M.; Najafi, F.; Javan, M. Polymerized nano-curcumin attenuates neurological symptoms in EAE model of multiple sclerosis through down regulation of inflammatory and oxidative processes and enhancing neuroprotection and myelin repair. Neuropharmacology 2015, 99, 156–167
Zhao, J.F.; Ching, L.C.; Huang, Y.C.; Chen, C.Y.; Chiang, A.N.; Kou, Y.R.; Shyue, S.K.; Lee, T.S. Molecular mechanism of curcumin on the suppression of cholesterol accumulation in macrophage foam cells and atherosclerosis. Mol. Nutr. Food Res. 2012, 56, 691–701.
Maurya, V.K.; Kumar, S.; Prasad, A.K.; Bhatt, M.L.B.; Saxena, S.K. 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, 179–193
Um, M.Y.; Hwang, K.H.; Choi, W.H.; Ahn, J.; Jung, C.H.; Ha, T.Y. Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits. Nutr. Res. 2014, 34, 886–893
Tabares-Guevara, J.H.; Jaramillo, J.C.; Ospina-Quintero, L.; Piedrahíta-Ochoa, C.A.; García-Valencia, N.; Bautista-Erazo, D.E.; Caro-Gómez, E.; Covián, C.; Retamal-Díaz, A.; Duarte, L.F.; et al. IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule. Front Immunol. 2021, 12
Lao, C.D.; Ruffin, M.T.; Normolle, D.; Heath, D.D.; Murray, S.I.; Bailey, J.M.; Boggs, M.E.; Crowell, J.; Rock, C.L.; Brenner, D.E. Dose escalation of a curcuminoid formulation. BMC Complement. Altern. Med. 2006, 6, 10.
Di Nunzio, M.; Valli, V.; Tomas-Cobos, L.; Tomas-Chisbert, T.; Murgui-Bosch, L.; Danesi, F.; Bordoni, A. Is cytotoxicity a determinant of the different in vitro and in vivo effects of bioactives? BMC Complement. Altern. Med. 2017, 17, 453
Cheng, A.L.; Hsu, C.H.; Lin, J.K.; Hsu, M.M.; Ho, Y.F.; Shen, T.S.; Ko, J.Y.; Lin, J.T.; Lin, B.R.; Ming-Shiang, W.; et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001, 21, 2895–2900
Díaz, F.J.; Aguilar-Jiménez, W.; Flórez-Álvarez, L.; Valencia, G.; Laiton-Donato, K.; Franco-Muñoz, C.; Álvarez-Díaz, D.; MercadoReyes, M.; Rugeles, M.T. Isolation and characterization of an early SARS-CoV-2 isolate from the 2020 epidemic in Medellín, Colombia. Biomédica 2020, 40, 148–158
Zouharova, D.; Lipenska, I.; Fojtikova, M.; Kulich, P.; Neca, J.; Slany, M.; Kovarcik, K.; Turanek-Knotigova, P.; Hubatka, F.; Celechovska, H.; et al. Antiviral activities of 2,6-diaminopurine-based acyclic nucleoside phosphonates against herpesviruses: In vitro study results with pseudorabies virus (PrV, SuHV-1). Vet. Microbiol. 2016, 184, 84–93.
Zapata-Cardona, M.I.; Flórez-Álvarez, L.; Zapata-Builes, W.; Guerra-Sandoval, A.L.; Guerra-Almonacid, C.M.; Hincapié-García, J.; Rugeles, M.T.; Hernandez, J.C. Atorvastatin effectively inhibits late replicative cycle steps of SARS-CoV-2 in vitro. bioRxiv 2021.
Uzunova, K.; Filipova, E.; Pavlova, V.; Vekov, T. Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. Biomed. Pharm. 2020, 131, 110668. [
Tandon, R.; Sharp, J.S.; Zhang, F.; Pomin, V.H.; Ashpole, N.M.; Mitra, D.; McCandless, M.G.; Jin, W.; Liu, H.; Sharma, P.; et al. Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives. J. Virol. 2021, 95
Marin-Palma, D.; Castro, G.A.; Cardona-Arias, J.A.; Urcuqui-Inchima, S.; Hernandez, J.C. Lower High-Density Lipoproteins Levels During Human Immunodeficiency Virus Type 1 Infection Are Associated with Increased Inflammatory Markers and Disease Progression. Front Immunol. 2018, 9, 1350
Marin-Palma, D.; Sirois, C.M.; Urcuqui-Inchima, S.; Hernandez, J.C. Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations. PLoS ONE 2019, 14, e0214245. [
Feria-Garzon, M.G.; Rugeles, M.T.; Hernandez, J.C.; Lujan, J.A.; Taborda, N.A. Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection. Int. J. Mol. Sci. 2019, 20, 4476.
dc.rights.license.none.fl_str_mv Atribución
dc.rights.accessrights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv Atribución
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 1-17
dc.coverage.temporal.spa.fl_str_mv 16;26
dc.publisher.spa.fl_str_mv Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado
dc.publisher.program.spa.fl_str_mv Medicina
dc.publisher.place.spa.fl_str_mv Medellín
institution Universidad Cooperativa de Colombia
bitstream.url.fl_str_mv https://repository.ucc.edu.co/bitstreams/12a240c9-138d-4c7a-9033-b52139419e9b/download
https://repository.ucc.edu.co/bitstreams/7560facd-f3fd-4298-8482-275549bb998a/download
https://repository.ucc.edu.co/bitstreams/e4f2c8cb-09a0-42b0-8057-e6e8b4c1249f/download
https://repository.ucc.edu.co/bitstreams/dd026258-dbd8-44ff-a5f4-14f60020dae6/download
bitstream.checksum.fl_str_mv 8630c8991658da157e0b29d11ca70fc6
3bce4f7ab09dfc588f126e1e36e98a45
5d4c25b69bb4ce75e6503978375418c5
3a17cfb9ca8c5f2a8cf17de979dfe843
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad Cooperativa de Colombia
repository.mail.fl_str_mv bdigital@metabiblioteca.com
_version_ 1811564980821032960
spelling Marín Palma, DamarizTabares Guevara, JorgeZapata Cardona, María IsabelFlórez Álvarez, LizdanyYepes, Lina M.Rugeles López, María TeresaZapata Builes, WildemanHernández López, Juan CarlosTaborda, Natalia Andrea16;262022-03-16T19:46:20Z2022-03-16T19:46:20Z2021-11-1610.3390/molecules26226900https://hdl.handle.net/20.500.12494/44426Marín-Palma D, Tabares-Guevara JH, Zapata-Cardona MI, Flórez-Álvarez L, Yepes LM, Rugeles MT, Zapata-Builes W, Hernandez JC, Taborda NA. (2021) Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms. Molecules. 2021 Nov 16;26(22):6900. doi: 10.3390/molecules26226900. http://hdl.handle.net/20.500.12494/44426Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound against SARS-CoV-2 was evaluated using four treatment strategies (i. pre–post infection treatment, ii. co-treatment, iii. pre-infection, and iv. post-infection). The D614G strain and Delta variant of SARS-CoV-2 were used, and the viral titer was quantified by plaque assay. The anti-inflammatory effect was evaluated in peripheral blood mononuclear cells (PBMCs) using qPCR and ELISA. By pre–post infection treatment, Curcumin (10 µg/mL) exhibited antiviral effect of 99% and 99.8% against DG614 strain and Delta variant, respectively. Curcumin also inhibited D614G strain by pre-infection and post-infection treatment. In addition, curcumin showed a virucidal effect against D614G strain and Delta variant. Finally, the pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) released by PBMCs triggered by SARS-CoV-2 were decreased after treatment with curcumin. Our results suggest that curcumin affects the SARS-CoV-2 replicative cycle and exhibits virucidal effect with a variant/strain independent antiviral effect and immune-modulatory properties. This is the first study that showed a combined (antiviral/anti-inflammatory) effect of curcumin during SARS-CoV-2 infection. However, additional studies are required to define its use as a treatment for the COVID-19.https://scienti.colciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000283088http://orcid.org/0000-0002-9200-5698https://scienti.colciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000011355juanc.hernandezl@campusucc.edu.co1-17Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y EnvigadoMedicinaMedellínhttps://www.mdpi.com/1420-3049/26/22/6900MoleculesZhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; et al. Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, 588Woo, P.C.; Lau, S.K.; Huang, Y.; Yuen, K.Y. Coronavirus diversity, phylogeny and interspecies jumping. Exp. Biol. Med. (Maywood) 2009, 234, 1117–1127Su, S.; Wong, G.; Shi, W.; Liu, J.; Lai, A.C.K.; Zhou, J.; Liu, W.; Bi, Y.; Gao, G.F. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol. 2016, 24, 490–502Forni, D.; Cagliani, R.; Clerici, M.; Sironi, M. Molecular Evolution of Human Coronavirus Genomes. Trends Microbiol. 2017, 25, 35–48.Malik, Y.A. Properties of Coronavirus and SARS-CoV-2. Malays. J. Pathol. 2020, 42, 3–11Sun, J.; He, W.T.; Wang, L.; Lai, A.; Ji, X.; Zhai, X.; Li, G.; Suchard, M.A.; Tian, J.; Zhou, J.; et al. COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives. Trends Mol. Med. 2020, 26, 483–495Du, L.; He, Y.; Zhou, Y.; Liu, S.; Zheng, B.J.; Jiang, S. The spike protein of SARS-CoV—A target for vaccine and therapeutic development. Nat. Rev. Microbiol. 2009, 7, 226–236.Walls, A.C.; Park, Y.J.; Tortorici, M.A.; Wall, A.; McGuire, A.T.; Veesler, D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020, 183, 1735Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; et al. Genomic characterisation and epidemiology of 2019 novel coronavirus:Implications for virus origins and receptor binding. Lancet 2020, 395, 565–574Ghanbari, R.; Teimoori, A.; Sadeghi, A.; Mohamadkhani, A.; Rezasoltani, S.; Asadi, E.; Jouyban, A.; Sumner, S.C. Existing antiviral options against SARS-CoV-2 replication in COVID-19 patients. Future Microbiol. 2020, 15, 1747–1758.Paces, J.; Strizova, Z.; Smrz, D.; Cerny, J. COVID-19 and the immune system. Physiol. Res. 2020, 69, 379–388Aguilar-Jiménez, W.; Flórez-Álvarez, L.; Rincón, D.S.; Marín-Palma, D.; Sánchez-Martínez, A.; Martínez, J.; Zapata, M.I.; Loaiza, J.D.; Cárdenas, C.; Guzmán, F.; et al. Caracterización inmunológica de un grupo familiar colombiano con infección por SARS-CoV-2. Biomedica 2021, 41, 86–102Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506.Xiong, Y.; Liu, Y.; Cao, L.; Wang, D.; Guo, M.; Jiang, A.; Guo, D.; Hu, W.; Yang, J.; Tang, Z.; et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg. Microbes Infect 2020, 9, 761–770Mani, J.S.; Johnson, J.B.; Steel, J.C.; Broszczak, D.A.; Neilsen, P.M.; Walsh, K.B.; Naiker, M. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020, 284, 197989Yepes-Perez, A.F.; Herrera-Calderon, O.; Oliveros, C.A.; Florez-Alvarez, L.; Zapata-Cardona, M.I.; Yepes, L.; Aguilar-Jimenez, W.; Rugeles, M.T.; Zapata, W. The Hydroalcoholic Extract of Uncaria tomentosa (Cat’s Claw) Inhibits the Infection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) In Vitro. Evid. Based Complement. Altern. Med. 2021, 2021, 6679761.Moghadamtousi, S.Z.; Kadir, H.A.; Hassandarvish, P.; Tajik, H.; Abubakar, S.; Zandi, K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed. Res. Int. 2014, 2014, 186864.Gupta, H.; Gupta, M.; Bhargava, S. Potential use of turmeric in COVID-19. Clin. Exp. Derm. 2020, 45, 902–903. [CrossRef] 19. Sahebkar, A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res. 2014, 28, 633–642Sahebkar, A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res. 2014, 28, 633–642.Ranjan, D.; Chen, C.; Johnston, T.D.; Jeon, H.; Nagabhushan, M. Curcumin inhibits mitogen stimulated lymphocyte proliferation, NFkappaB activation, and IL-2 signaling. J. Surg. Res. 2004, 121, 171–177.Gong, Z.; Zhou, J.; Li, H.; Gao, Y.; Xu, C.; Zhao, S.; Chen, Y.; Cai, W.; Wu, J. Curcumin suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock. Mol. Nutr. Food Res. 2015, 59, 2132–2142.Yin, H.; Guo, Q.; Li, X.; Tang, T.; Li, C.; Wang, H.; Sun, Y.; Feng, Q.; Ma, C.; Gao, C.; et al. Curcumin Suppresses IL-1beta Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome. J. Immunol. 2018, 200, 2835–2846.Balasubramanian, A.; Pilankatta, R.; Teramoto, T.; Sajith, A.M.; Nwulia, E.; Kulkarni, A.; Padmanabhan, R. Inhibition of dengue virus by curcuminoids. Antivir. Res. 2019, 162, 71–78.Mounce, B.C.; Cesaro, T.; Carrau, L.; Vallet, T.; Vignuzzi, M. Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding. Antivir. Res. 2017, 142, 148–157.Richart, S.M.; Li, Y.L.; Mizushina, Y.; Chang, Y.Y.; Chung, T.Y.; Chen, G.H.; Tzen, J.T.; Shia, K.S.; Hsu, W.L. Synergic effect of curcumin and its structural analogue (Monoacetylcurcumin) on anti-influenza virus infection. J. Food Drug Anal. 2018, 26, 1015–1023.Mazumder, A.; Raghavan, K.; Weinstein, J.; Kohn, K.W.; Pommier, Y. Inhibition of human immunodeficiency virus type-1 integrase by curcumin. Biochem. Pharm. 1995, 49, 1165–1170.Ali, A.; Banerjea, A.C. Curcumin inhibits HIV-1 by promoting Tat protein degradation. Sci. Rep. 2016, 6, 27539Jena, A.B.; Kanungo, N.; Nayak, V.; Chainy, G.B.N.; Dandapat, J. Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane:Insights from computational studies. Sci. Rep. 2021, 11, 2043.Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Kruger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020, 181, 271–280Padmanabhan, P.; Desikan, R.; Dixit, N.M. Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARSCoV-2 infection. PLoS Comput. Biol. 2020, 16, e1008461.Praditya, D.; Kirchhoff, L.; Bruning, J.; Rachmawati, H.; Steinmann, J.; Steinmann, E. Anti-infective Properties of the Golden Spice Curcumin. Front Microbiol. 2019, 10, 912Korber, B.; Fischer, W.M.; Gnanakaran, S.; Yoon, H.; Theiler, J.; Abfalterer, W.; Hengartner, N.; Giorgi, E.E.; Bhattacharya, T.; Foley, B.; et al. Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell 2020, 182, 812–827.e819Khateeb, J.; Li, Y.; Zhang, H. Emerging SARS-CoV-2 variants of concern and potential intervention approaches. Crit. Care 2021, 25, 244.Trujillo-Correa, A.I.; Quintero-Gil, D.C.; Diaz-Castillo, F.; Quiñones, W.; Robledo, S.M.; Martinez-Gutierrez, M. In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting. BMC Complement. Altern. Med. 2019, 19, 298.Chen, D.-Y.; Shien, J.-H.; Tiley, L.; Chiou, S.-S.; Wang, S.-Y.; Chang, T.-J.; Lee, Y.-J.; Chan, K.-W.; Hsu, W.-L. Curcumin inhibits influenza virus infection and haemagglutination activity. Food Chem. 2010, 119, 1346–1351. [Chen, T.Y.; Chen, D.Y.; Wen, H.W.; Ou, J.L.; Chiou, S.S.; Chen, J.M.; Wong, M.L.; Hsu, W.L. Inhibition of enveloped viruses infectivity by curcumin. PLoS ONE 2013, 8, e62482.Zandi, K.; Teoh, B.T.; Sam, S.S.; Wong, P.F.; Mustafa, M.R.; Abubakar, S. Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol. J. 2011, 8, 560Kandeel, M.; Al-Nazawi, M. Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease. Life Sci. 2020, 251, 117627.Katta, S.; Srivastava, A.; Thangapazham, R.L.; Rosner, I.L.; Cullen, J.; Li, H.; Sharad, S. Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells. Int. J. Mol. Sci. 2019, 20, 4891. [Yang, X.X.; Li, C.M.; Huang, C.Z. Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection. Nanoscale 2016, 8, 3040–3048.Wu, J.; Hou, W.; Cao, B.; Zuo, T.; Xue, C.; Leung, A.W.; Xu, C.; Tang, Q.J. Virucidal efficacy of treatment with photodynamically activated curcumin on murine norovirus bio-accumulated in oysters. Photodiagnosis. Photodyn. 2015, 12, 385–392.Tang, T.; Bidon, M.; Jaimes, J.A.; Whittaker, G.R.; Daniel, S. Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antivir. Res. 2020, 178, 104792Koch, J.; Uckeley, Z.M.; Doldan, P.; Stanifer, M.; Boulant, S.; Lozach, P.-Y. Host Cell Proteases Drive Early or Late SARS-CoV-2 Penetration. bioRxiv 2020. [Nagahama, K.; Utsumi, T.; Kumano, T.; Maekawa, S.; Oyama, N.; Kawakami, J. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency. Sci. Rep. 2016, 6, 30962Wen, C.C.; Kuo, Y.H.; Jan, J.T.; Liang, P.H.; Wang, S.Y.; Liu, H.G.; Lee, C.K.; Chang, S.T.; Kuo, C.J.; Lee, S.S.; et al. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. J. Med. Chem. 2007, 50, 4087–4095.Obata, K.; Kojima, T.; Masaki, T.; Okabayashi, T.; Yokota, S.; Hirakawa, S.; Nomura, K.; Takasawa, A.; Murata, M.; Tanaka, S.; et al. Curcumin prevents replication of respiratory syncytial virus and the epithelial responses to it in human nasal epithelial cells. PLoS ONE 2013, 8, e70225.Mathew, D.; Hsu, W.-L. Antiviral potential of curcumin. J. Funct. Foods 2018, 40, 692–699. [Khaerunnisa, S.K.H.; Awaluddin, R.; Suhartati, S.; Soetjipto, S. Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study. Preprints 2020.Kumar, M.; Sodhi, K.K.; Singh, D.K. Addressing the potential role of curcumin in the prevention of COVID-19 by targeting the Nsp9 replicase protein through molecular docking. Arch. Microbiol. 2021, 203, 1691–1696Planas, D.; Veyer, D.; Baidaliuk, A.; Staropoli, I.; Guivel-Benhassine, F.; Rajah, M.M.; Planchais, C.; Porrot, F.; Robillard, N.; Puech, J.; et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 2021, 596, 276–280.Du, T.; Nan, Y.; Xiao, S.; Zhao, Q.; Zhou, E.M. Antiviral Strategies against PRRSV Infection. Trends Microbiol. 2017, 25, 968–979.Lopez Bernal, J.; Andrews, N.; Gower, C.; Gallagher, E.; Simmons, R.; Thelwall, S.; Stowe, J.; Tessier, E.; Groves, N.; Dabrera, G.; et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N. Engl. J. Med. 2021, 385, 585–594.Blanco-Melo, D.; Nilsson-Payant, B.E.; Liu, W.C.; Uhl, S.; Hoagland, D.; Moller, R.; Jordan, T.X.; Oishi, K.; Panis, M.; Sachs, D.; et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell 2020, 181, 1036–1045.Hirano, T.; Murakami, M. COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome. Immunity 2020, 52, 731–733Vardhana, S.A.; Wolchok, J.D. The many faces of the anti-COVID immune response. J. Exp. Med. 2020, 217Valizadeh, H.; Abdolmohammadi-Vahid, S.; Danshina, S.; Ziya Gencer, M.; Ammari, A.; Sadeghi, A.; Roshangar, L.; Aslani, S.; Esmaeilzadeh, A.; Ghaebi, M.; et al. Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients. Int. Immunol. 2020, 89, 107088Haneklaus, M.; O’Neill, L.A. NLRP3 at the interface of metabolism and inflammation. Immunol. Rev. 2015, 265, 53–62.Zhang, S.; Zou, J.; Li, P.; Zheng, X.; Feng, D. Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by Inhibiting Toll-like Receptor 4 Expression. J. Agric. Food Chem. 2018, 66, 449–456Xu, Y.; Liu, L. Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF-kappaB signaling pathway. Influenza Other Respir. Viruses 2017, 11, 457–463Hasanzadeh, S.; Read, M.I.; Bland, A.R.; Majeed, M.; Jamialahmadi, T.; Sahebkar, A. Curcumin: An inflammasome silencer. Pharm. Res. 2020, 159, 104921Dai, Q.; Zhou, D.; Xu, L.; Song, X. Curcumin alleviates rheumatoid arthritis-induced inflammation and synovial hyperplasia by targeting mTOR pathway in rats. Drug Des. Devel. 2018, 12, 4095–4105Hasan, S.T.; Zingg, J.M.; Kwan, P.; Noble, T.; Smith, D.; Meydani, M. Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice. Atherosclerosis 2014, 232, 40–51.Lim, G.P.; Chu, T.; Yang, F.; Beech, W.; Frautschy, S.A.; Cole, G.M. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Neurosci. 2001, 21, 8370–8377Mohajeri, M.; Sadeghizadeh, M.; Najafi, F.; Javan, M. Polymerized nano-curcumin attenuates neurological symptoms in EAE model of multiple sclerosis through down regulation of inflammatory and oxidative processes and enhancing neuroprotection and myelin repair. Neuropharmacology 2015, 99, 156–167Zhao, J.F.; Ching, L.C.; Huang, Y.C.; Chen, C.Y.; Chiang, A.N.; Kou, Y.R.; Shyue, S.K.; Lee, T.S. Molecular mechanism of curcumin on the suppression of cholesterol accumulation in macrophage foam cells and atherosclerosis. Mol. Nutr. Food Res. 2012, 56, 691–701.Maurya, V.K.; Kumar, S.; Prasad, A.K.; Bhatt, M.L.B.; Saxena, S.K. 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, 179–193Um, M.Y.; Hwang, K.H.; Choi, W.H.; Ahn, J.; Jung, C.H.; Ha, T.Y. Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits. Nutr. Res. 2014, 34, 886–893Tabares-Guevara, J.H.; Jaramillo, J.C.; Ospina-Quintero, L.; Piedrahíta-Ochoa, C.A.; García-Valencia, N.; Bautista-Erazo, D.E.; Caro-Gómez, E.; Covián, C.; Retamal-Díaz, A.; Duarte, L.F.; et al. IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule. Front Immunol. 2021, 12Lao, C.D.; Ruffin, M.T.; Normolle, D.; Heath, D.D.; Murray, S.I.; Bailey, J.M.; Boggs, M.E.; Crowell, J.; Rock, C.L.; Brenner, D.E. Dose escalation of a curcuminoid formulation. BMC Complement. Altern. Med. 2006, 6, 10.Di Nunzio, M.; Valli, V.; Tomas-Cobos, L.; Tomas-Chisbert, T.; Murgui-Bosch, L.; Danesi, F.; Bordoni, A. Is cytotoxicity a determinant of the different in vitro and in vivo effects of bioactives? BMC Complement. Altern. Med. 2017, 17, 453Cheng, A.L.; Hsu, C.H.; Lin, J.K.; Hsu, M.M.; Ho, Y.F.; Shen, T.S.; Ko, J.Y.; Lin, J.T.; Lin, B.R.; Ming-Shiang, W.; et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001, 21, 2895–2900Díaz, F.J.; Aguilar-Jiménez, W.; Flórez-Álvarez, L.; Valencia, G.; Laiton-Donato, K.; Franco-Muñoz, C.; Álvarez-Díaz, D.; MercadoReyes, M.; Rugeles, M.T. Isolation and characterization of an early SARS-CoV-2 isolate from the 2020 epidemic in Medellín, Colombia. Biomédica 2020, 40, 148–158Zouharova, D.; Lipenska, I.; Fojtikova, M.; Kulich, P.; Neca, J.; Slany, M.; Kovarcik, K.; Turanek-Knotigova, P.; Hubatka, F.; Celechovska, H.; et al. Antiviral activities of 2,6-diaminopurine-based acyclic nucleoside phosphonates against herpesviruses: In vitro study results with pseudorabies virus (PrV, SuHV-1). Vet. Microbiol. 2016, 184, 84–93.Zapata-Cardona, M.I.; Flórez-Álvarez, L.; Zapata-Builes, W.; Guerra-Sandoval, A.L.; Guerra-Almonacid, C.M.; Hincapié-García, J.; Rugeles, M.T.; Hernandez, J.C. Atorvastatin effectively inhibits late replicative cycle steps of SARS-CoV-2 in vitro. bioRxiv 2021.Uzunova, K.; Filipova, E.; Pavlova, V.; Vekov, T. Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. Biomed. Pharm. 2020, 131, 110668. [Tandon, R.; Sharp, J.S.; Zhang, F.; Pomin, V.H.; Ashpole, N.M.; Mitra, D.; McCandless, M.G.; Jin, W.; Liu, H.; Sharma, P.; et al. Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives. J. Virol. 2021, 95Marin-Palma, D.; Castro, G.A.; Cardona-Arias, J.A.; Urcuqui-Inchima, S.; Hernandez, J.C. Lower High-Density Lipoproteins Levels During Human Immunodeficiency Virus Type 1 Infection Are Associated with Increased Inflammatory Markers and Disease Progression. Front Immunol. 2018, 9, 1350Marin-Palma, D.; Sirois, C.M.; Urcuqui-Inchima, S.; Hernandez, J.C. Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations. PLoS ONE 2019, 14, e0214245. [Feria-Garzon, M.G.; Rugeles, M.T.; Hernandez, J.C.; Lujan, J.A.; Taborda, N.A. Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection. Int. J. Mol. Sci. 2019, 20, 4476.CurcuminAntiviralCOVID-19SARS-CoV-2Immune responseInflammationD614G strainDelta variantCurcumin inhibits in vitro SARS-CoV-2 infection in Vero E6 cells through multiple antiviral mechanismsArtículos Científicoshttp://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAtribucióninfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationORIGINALCurcumin SARS-CoV-2.pdfCurcumin SARS-CoV-2.pdfArtículoapplication/pdf24466426https://repository.ucc.edu.co/bitstreams/12a240c9-138d-4c7a-9033-b52139419e9b/download8630c8991658da157e0b29d11ca70fc6MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-84334https://repository.ucc.edu.co/bitstreams/7560facd-f3fd-4298-8482-275549bb998a/download3bce4f7ab09dfc588f126e1e36e98a45MD52THUMBNAILCurcumin SARS-CoV-2.pdf.jpgCurcumin SARS-CoV-2.pdf.jpgGenerated Thumbnailimage/jpeg5804https://repository.ucc.edu.co/bitstreams/e4f2c8cb-09a0-42b0-8057-e6e8b4c1249f/download5d4c25b69bb4ce75e6503978375418c5MD53TEXTCurcumin SARS-CoV-2.pdf.txtCurcumin SARS-CoV-2.pdf.txtExtracted texttext/plain64669https://repository.ucc.edu.co/bitstreams/dd026258-dbd8-44ff-a5f4-14f60020dae6/download3a17cfb9ca8c5f2a8cf17de979dfe843MD5420.500.12494/44426oai:repository.ucc.edu.co:20.500.12494/444262024-08-10 22:47:41.306restrictedhttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.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