The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19—Results from a pragmatic randomized clinical trial
Ikram Din Ujjan, Saeed Khan, Roohi Nigar, Hammad Ahmed, Sagheer Ahmad, Amjad Khan
Frontiers in Nutrition, doi:10.3389/fnut.2022.1023997
A (2023) The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19-Results from a pragmatic randomized clinical trial.
Ethics statement The study was approved by the Research Ethics Committee (REC), Liaquat University of Medical and Health Sciences (LUMHS), Jamshoro, Pakistan via Ref. No. LUMHS/REC/-137. The patients/participants provided their written informed consent to participate in this study.
Author contributions IU: study design, data collection, data interpretation, supervision, and critical revision of the manuscript. SK: study design, data interpretation, and manuscript revision. RN: data collection, supervision, and manuscript revision. HA: study administration, data collection, and manuscript
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Aggarwal, Harikumar, Potential therapeutic effects of curcumin, the antiinflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases, Int J Biochem Cell Biol,
doi:10.1016/j.biocel.2008.06.010
Ahmadi, Salari, Sharifi, Reihani, Rostamiani et al., Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: a randomized triple-blind placebo-controlled clinical trial, Food Sci Nutr,
doi:10.1002/fsn3.2226
Babaei, Nassiri-Asl, Hosseinzadeh, Curcumin (a constituent of turmeric): new treatment option against COVID-19, Food Sci Nutr,
doi:10.1002/fsn3.1858
Bernal, Da Silva, Musungaie, Kovalchuk, Gonzalez, None
Biancatelli, Berrill, Catravas, Marik, Derosa et al., Antiviral, immunomodulatory, and anticoagulant effects of quercetin and its derivatives: potential role in prevention and management of COVID-19, Front Immunol,
doi:10.1016/j.jpha.2021.09.009
Bormann, Alt, Schipper, Van De Sand, Le-Trilling et al., Turmeric root and its bioactive ingredient curcumin effectively neutralize SARS-CoV-2 in vitro, Viruses,
doi:10.3390/v13101914
Chabot, Huntwork, Honarkar ; Shafie, Taheri, Alijani et al., Effect of nanocurcumin supplementation on the severity of symptoms and length of hospital stay in patients with COVID-19: a randomized double-blind placebo-controlled trial, Phytother Res,
doi:10.1002/ptr.7374
Chen, Li, Luo, Liu, Xu et al., Binding interaction of quercetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): structure-activity relationship studies reveal salient pharmacophore features, Bioorg Med Chem,
doi:10.1016/j.bmc.2006.09.014
Core, R: a language and environment for statistical computing
Docherty, Harrison, Green, Hardwick, Pius et al., Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO clinical characterisation protocol: prospective observational cohort study, BMJ,
doi:10.1136/bmj.m1985
Dorward, Russell, Um, Elshani, Armstrong et al., Tissue-specific immunopathology in fatal COVID-19, Am J Respir Crit Care Med,
doi:10.1164/rccm.202008-3265OC
Grasselli, Zangrillo, Zanella, Antonelli, Cabrini et al., Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the lombardy region, Italy, JAMA,
doi:10.1001/jama.2020.5394
Group, Tocilizumab in patients admitted to hospital with COVID-19: a randomised, controlled, open-label, platform trial, Lancet,
doi:10.1016/S0140-673600676-0
Gupta, Gonzalez-Rojas, Juarez, Casal, Moya et al., Early treatment for covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab, N Engl J Med,
doi:10.1056/NEJMoa2107934
Hammond, Leister-Tebbe, Gardner, Abreu, Wisemandle, Oral nirmatrelvir for high-risk, nonhospitalized adults with covid-19, N Engl J Med,
doi:10.1056/NEJMoa2118542
Harwood, Danielewska-Nikiel, Borzelleca, Flamm, Williams et al., A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties, Food Chem Toxicol,
doi:10.1016/j.fct.2007.05.015
Kalil, Patterson, Mehta, Tomashek, Wolfe et al., Baricitinib plus remdesivir for hospitalized adults with covid-19, N Engl J Med,
doi:10.1056/NEJMoa2031994
Kamel, Abdelseed, Albalawi, Aslsalameen, Almutairi et al., Treatment of COVID-19 patients with quercetin: a prospective, single center, randomized, controlled trial, Turk J Biol,
doi:10.3906/biy-2104-16
Khursheed, Singh, Wadhwa, Gulati, Awasthi, Enhancing the potential preclinical and clinical benefits of quercetin through novel drug delivery systems, Drug Discovery Today,
doi:10.1016/j.drudis.2019.11.001
Lee, Yu, Trimpert, Benthani, Mairhofer et al., Virus-induced senescence is a driver and therapeutic target in COVID-19, Nature,
doi:10.1038/s41586-021-03995-1
Leka, Hamann, Desdemoustier, Frédérich, Garigliany et al., In vitro antiviral activity against SARS-CoV-2 of common herbal medicinal extracts and their bioactive compounds, Phytother Res,
doi:10.3390/molecules26226900
Lelli, Sahebkar, Johnston, Pedone, Curcumin use in pulmonary diseases: state of the art and future perspectives, Pharmacol Res,
doi:10.1016/j.phrs.2016.11.017
Lucas, Wong, Klein, Castro, Silva et al., Longitudinal analyses reveal immunological misfiring in severe COVID-19, Nature,
doi:10.1038/s41586-020-2588-y
Majeed, Nagabhushanam, Shah, Mundkur, A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of a nutritional supplement (ImmuActive(TM)) for COVID-19 patients, Evid Based Complement Alternat Med,
doi:10.1155/2021/8447545
Moderbacher, Ramirez, Grifoni, Hastie, Weiskopf, Antigen-specific adaptive immunity to SARS-CoV-2 in Acute COVID-19 and associations with age and disease severity, Cell,
doi:10.1016/j.cell.2020.09.038
Moghadamtousi, Kadir, Hassandarvish, Tajik, Abubakar et al., Review on antibacterial, antiviral, and antifungal activity of curcumin, BioMed Res Int,
doi:10.1155/2014/186864
Munafò, Donati, Brindani, Ottonello, Armirotti et al., Quercetin and luteolin are single-digit micromolar inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase, Sci Rep,
doi:10.1038/s41598-022-14664-2
Nguyen, Woo, Kang, Nguyen, Kim et al., Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris, Biotechnol Lett,
doi:10.1007/s10529-011-0845-8
Pan, Fang, Zhang, Pan, Liu et al., Chinese herbal compounds against SARS-CoV-2: puerarin and quercetin impair the binding of viral S-protein to ACE2 receptor, Comput Struct Biotechnol J,
doi:10.1016/j.csbj.2020.11.010
Pawar, Mastud, Pawar, Pawar, Bhoite et al., A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients, Int Immunopharmacol,
doi:10.1016/j.intimp.2020.107088
Petrillo, Orrù, Fais, Fantini, ; Abian et al., Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening, Int J Biol Macromol,
doi:10.1016/j.ijbiomac.2020.07.235
Pierro, Derosa, Maffioli, Bertuccioli, Togni et al., Possible therapeutic effects of adjuvant quercetin supplementation against early-stage COVID-19 infection: a prospective, randomized, controlled, and open-label study, Int J Gen Med,
doi:10.2147/IJGM.S318949
Richardson, Hirsch, Narasimhan, Crawford, Mcginn et al., Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area, JAMA,
doi:10.1001/jama.2020.6775
Rizzuti, Grande, Conforti, Jimenez-Alesanco, Ceballos-Laita et al., Rutin is a low micromolar inhibitor of SARS-CoV-2 main protease 3CLpro: implications for drug design of quercetin analogs, Biomedicines,
doi:10.3390/biomedicines9040375
Rondanelli, Perna, Gasparri, Petrangolini, Allegrini et al., Promising effects of 3-month period of quercetin phytosome((R)) supplementation in the prevention of symptomatic COVID-19 disease in healthcare workers: a pilot study, Life,
doi:10.3390/life12010066
Shohan, Nashibi, Mahmoudian-Sani, Abolnezhadian, Ghafourian et al., Oral co-supplementation of curcumin, quercetin, and vitamin D3 as an adjuvant therapy for mild to moderate symptoms of COVID-19-results from a pilot open-label, randomized controlled trial, Zaporizhia Med J,
doi:10.3389/fphar.2022.898062
Weinreich, Sivapalasingam, Norton, Ali, Gao et al., REGN-COV2, a neutralizing antibody cocktail, in outpatients with covid-19, N Engl J Med,
doi:10.1056/NEJMoa2035002
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/jm070295s
Yang, Wang, Long, Li, Quercetin: its main pharmacological activity and potential application in clinical medicine, Oxid Med Cell Longev,
doi:10.1155/2020/8825387
Yang, Xie, Tu, Fu, Xu et al., The signal pathways and treatment of cytokine storm in COVID-19, Signal Trans Target Ther,
doi:10.1038/s41392-021-00679-0
Zahedipour, Hosseini, Sathyapalan, Majeed, Jamialahmadi et al., Antiviral and immunomodulatory activity of curcumin: a case for prophylactic therapy for COVID-19, Front Pharmacol,
doi:10.1016/j.heliyon.2021.e06350