Turmeric Root and Its Bioactive Ingredient Curcumin Effectively Neutralize SARS-CoV-2 In Vitro
Maren Bormann, Mira Alt, Leonie Schipper, Lukas Van De Sand, Vu Thuy Khanh Le-Trilling, Lydia Rink, Natalie Heinen, Rabea Julia Madel, Mona Otte, Korbinian Wuensch, Christiane Silke Heilingloh, Thorsten Mueller, Ulf Dittmer, Carina Elsner, Stephanie Pfaender, Mirko Trilling, Oliver Witzke, Adalbert Krawczyk
Viruses, doi:10.3390/v13101914
Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 . The availability of effective and well-tolerated antiviral drugs for the treatment of COVID-19 patients is still very limited. Traditional herbal medicines elicit antiviral activity against various viruses and might therefore represent a promising option for the complementary treatment of COVID-19 patients. The application of turmeric root in herbal medicine has a very long history. Its bioactive ingredient curcumin shows a broad-spectrum antimicrobial activity. In the present study, we investigated the antiviral activity of aqueous turmeric root extract, the dissolved content of a curcumin-containing nutritional supplement capsule, and pure curcumin against SARS-CoV-2. Turmeric root extract, dissolved turmeric capsule content, and pure curcumin effectively neutralized SARS-CoV-2 at subtoxic concentrations in Vero E6 and human Calu-3 cells. Furthermore, curcumin treatment significantly reduced SARS-CoV-2 RNA levels in cell culture supernatants. Our data uncover curcumin as a promising compound for complementary COVID-19 treatment. Curcumin concentrations contained in turmeric root or capsules used as nutritional supplements completely neutralized SARS-CoV-2 in vitro. Our data argue in favor of appropriate and carefully monitored clinical studies that vigorously test the effectiveness of complementary treatment of COVID-19 patients with curcumin-containing products.
References
Abdollahi, Momtazi, Johnston, Sahebkar, Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: A nature-made jack-of-all-trades?, J. Cell. Physiol,
doi:10.1002/jcp.25778Abidi, Gupta, Agarwal, Bhalla, Saluja, Evaluation of Efficacy of Curcumin as an Add-on therapy in Patients of Bronchial Asthma, J. Clin. Diagn. Res,
doi:10.7860/JCDR/2014/9273.4705Bandyopadhyay, Farmer to pharmacist: Curcumin as an anti-invasive and antimetastatic agent for the treatment of cancer, Front. Chem,
doi:10.3389/fchem.2014.00113Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the Treatment of Covid-19-Final Report, N. Engl. J. Med,
doi:10.1056/NEJMoa2007764Chainani-Wu, Safety and Anti-Inflammatory Activity of Curcumin: A Component of Tumeric (Curcuma longa), J. Altern. Complement. Med,
doi:10.1089/107555303321223035Cheng, Hsu, Lin, Hsu, Ho et al., Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions, Anticancer Res
Colpitts, Schang, Rachmawati, Frentzen, Pfaender et al., Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells, Gut,
doi:10.1136/gutjnl-2012-304299Daily, Yang, Park, Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials, J. Med. Food,
doi:10.1089/jmf.2016.3705Derosa, Maffioli, Simental-Mendía, Bo, Sahebkar, Effect of curcumin on circulating interleukin-6 concentrations: A systematic review and meta-analysis of randomized controlled trials, Pharmacol. Res,
doi:10.1016/j.phrs.2016.07.004Guan, Ni, Hu, Liang, Ou et al., Clinical Characteristics of Coronavirus Disease 2019 in China, N. Engl. J. Med,
doi:10.1056/NEJMoa2002032Heilingloh, Aufderhorst, Schipper, Dittmer, Witzke et al., Susceptibility of SARS-CoV-2 to UV irradiation, Am. J. Infect. Control,
doi:10.1016/j.ajic.2020.07.031Hoffmann, Mösbauer, Hofmann-Winkler, Kaul, Kleine-Weber et al., Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2, CrossRef,
doi:10.1038/s41586-020-2575-3Horby, Lim, Emberson, Mafham, Bell et al., Dexamethasone in Hospitalized Patients with Covid-19, N. Engl. J. Med
Ireson, Orr, Jones, Verschoyle, Lim et al., Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production, Cancer Res
Jahanbakhshi, Maleki Dana, Badehnoosh, Yousefi, Mansournia et al., Curcumin anti-tumor effects on endometrial cancer with focus on its molecular targets, Cancer Cell Int,
doi:10.1186/s12935-021-01832-zJena, Kanungo, Nayak, Chainy, Dandapat, Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane: Insights from computational studies, Sci. Rep,
doi:10.1038/s41598-021-81462-7Krah, A simplified multiwell plate assay for the measurement of hepatitis A virus infectivity, Biologicals
Kunnumakkara, Bordoloi, Padmavathi, Monisha, Roy et al., Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases, Br. J. Pharmacol,
doi:10.1111/bph.13621Lao, Ruffin, Normolle, Heath, Murray et al., Dose escalation of a curcuminoid formulation, BMC Complement. Altern. Med,
doi:10.1186/1472-6882-6-10Le-Trilling, Mennerich, Schuler, Flores-Martinez, Katschinski et al., Universally available herbal teas based on sage and perilla elicit potent antiviral activity against SARS-CoV-2 in vitro, bioRxiv,
doi:10.1101/2020.11.18.388710Lindemann, Lenz, Knop, Klump, Alt et al., Convalescent plasma treatment of critically ill intensive care COVID-19 patients, Transfusion,
doi:10.1111/trf.16392Lutter, Scholka, Richter, Anderer, Applying XTT, WST-1, and WST-8 to human chondrocytes: A comparison of membrane-impermeable tetrazolium salts in 2D and 3D cultures, Clin. Hemorheol. Microcirc,
doi:10.3233/CH-179213Mani, Johnson, Steel, Broszczak, Neilsen et al., Natural product-derived phytochemicals as potential agents against coronaviruses: A review, Virus Res,
doi:10.1016/j.virusres.2020.197989Moghadamtousi, Kadir, Hassandarvish, Tajik, Abubakar et al., A review on antibacterial, antiviral, and antifungal activity of curcumin, BioMed Res. Int
Nabavi, Daglia, Moghaddam, Habtemariam, Nabavi, Curcumin and Liver Disease: From Chemistry to Medicine, Compr. Rev. Food Sci. Food Saf,
doi:10.1111/1541-4337.12047Pan, Huang, Lin, Biotransformation of curcumin through reduction and glucuronidation in mice, Drug Metab. Dispos
Perrone, Ardito, Giannatempo, Dioguardi, Troiano et al., Biological and therapeutic activities, and anticancer properties of curcumin, Exp. Ther. Med,
doi:10.3892/etm.2015.2749Pivari, Mingione, Brasacchio, Soldati, Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment, Nutrients,
doi:10.3390/nu11081837Praditya, Kirchhoff, Brüning, Rachmawati, Steinmann et al., Anti-infective Properties of the Golden Spice Curcumin, Front. Microbiol,
doi:10.3389/fmicb.2019.00912Prasad, Aggarwal, Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine
Sahebkar, Cicero, Simental-Mendía, Aggarwal, Gupta, Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials, Pharmacol. Res,
doi:10.1016/j.phrs.2016.03.026Schöler, Le-Trilling, Eilbrecht, Mennerich, Anastasiou et al., A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds, Front. Immunol,
doi:10.3389/fimmu.2020.573526Shanmugarajan, Prabitha, Kumar, Suresh, Curcumin to inhibit binding of spike glycoprotein to ACE2 receptors: Computational modelling, simulations, and ADMET studies to explore curcuminoids against novel SARS-CoV-2 targets, RSC Adv,
doi:10.1039/D0RA03167DShoba, Joy, Joseph, Majeed, Rajendran et al., Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers, Planta Med,
doi:10.1055/s-2006-957450Toptan, Hoehl, Westhaus, Bojkova, Berger et al., Optimized qRT-PCR Approach for the Detection of Intra-and Extra-Cellular SARS-CoV-2 RNAs, Int. J. Mol. Sci,
doi:10.3390/ijms21124396Van De Sand, Bormann, Alt, Schipper, Heilingloh et al., Glycyrrhizin Effectively Inhibits SARS-CoV-2 Replication by Inhibiting the Viral Main Protease, Viruses
Wen, Kuo, Jan, Liang, Wang et al., Specific Plant Terpenoids and Lignoids Possess Potent Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus, J. Med. Chem,
doi:10.1021/jm070295sZahedipour, Hosseini, Sathyapalan, Majeed, Jamialahmadi et al., Potential effects of curcumin in the treatment of COVID-19 infection, Phytother. Res,
doi:10.1002/ptr.6738Ziegler, Allon, Nyquist, Mbano, Miao et al., SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues, Cell,
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"DOI": "10.1016/j.phrs.2016.03.026",
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},
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"DOI": "10.1016/j.phrs.2016.07.004",
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"key": "ref38",
"series-title": "GRAS Notice 000460: Curcuminoids Purified from Turmeric (Curcuma longa L.)",
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"key": "ref39",
"series-title": "Scientific Opinion on the Re-Evaluation of Curcumin (E 100) as a Food Additive",
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"key": "ref40",
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"author": "Ireson",
"first-page": "1058",
"journal-title": "Cancer Res.",
"key": "ref43",
"volume": "61",
"year": "2001"
},
{
"article-title": "Biotransformation of curcumin through reduction and glucuronidation in mice",
"author": "Pan",
"first-page": "486",
"journal-title": "Drug Metab. Dispos.",
"key": "ref44",
"volume": "27",
"year": "1999"
},
{
"DOI": "10.1111/j.1600-0773.1978.tb02240.x",
"doi-asserted-by": "publisher",
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{
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"key": "ref46"
},
{
"DOI": "10.1055/s-2006-957450",
"doi-asserted-by": "publisher",
"key": "ref47"
},
{
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