Conv. Plasma
Nigella Sativa
Peg.. Lambda

All curcumin studies
Meta analysis
Home COVID-19 treatment researchCurcuminCurcumin (more..)
Melatonin Meta
Bromhexine Meta Metformin Meta
Budesonide Meta
Cannabidiol Meta Molnupiravir Meta
Colchicine Meta
Conv. Plasma Meta
Curcumin Meta Nigella Sativa Meta
Ensovibep Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Peg.. Lambda Meta
Fluvoxamine Meta Quercetin Meta
Hydroxychlor.. Meta Remdesivir Meta
Ivermectin Meta
Lactoferrin Meta

All Studies   Meta Analysis   Recent:  

Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions

Goc et al., PLOS ONE, doi:10.1371/journal.pone.0253489
Jun 2021  
  Source   PDF   All Studies   Meta AnalysisMeta
In Vitro study of 56 polyphenols showing that curcumin has high binding affinity to the RBD of the SARS-CoV-2 spike protein, inhibits ACE2 at non-toxic concentrations, and decreases activity of TMPRSS2. Promising results were also seen for brazilin and theaflavin-3,3’-digallate.
Goc et al., 17 Jun 2021, peer-reviewed, 4 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
All Studies   Meta Analysis   Submit Updates or Corrections
This PaperCurcuminAll
Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions
Anna Goc, Waldemar Sumera, Matthias Rath, Aleksandra Niedzwiecki
PLOS ONE, doi:10.1371/journal.pone.0253489
In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3'-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3,3'-digallate at 25 μg/ml and curcumin above 10 μg/ml concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at the same time its activity in both cell-free and cell-based assays. Our study also demonstrates that brazilin and theaflavin-3,3'-digallate, and to a still greater extent, curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and cell-based assays. Similar pattern was observed with cathepsin L, although only theaflavin-3,3'-digallate showed a modest diminution of cathepsin L expression at protein level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific polyphenols and their prospects for further scientific and clinical investigations.
Supporting information S1 File. Raw Western blot images. (PPTX) Author Contributions Conceptualization: Anna Goc. Data curation: Matthias Rath, Aleksandra Niedzwiecki. Formal analysis: Anna Goc, Waldemar Sumera. Visualization: Anna Goc, Waldemar Sumera, Aleksandra Niedzwiecki. Writing -original draft: Anna Goc, Waldemar Sumera, Matthias Rath, Aleksandra Niedzwiecki. Writing -review & editing: Anna Goc, Waldemar Sumera, Aleksandra Niedzwiecki.
Anggakusuma, Colpitts, Schang, Rachmawati, Frentzen et al., Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells, Gut, doi:10.1136/gutjnl-2012-304299
Belouzard, Chu, Whittaker, Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinctsites, Proc Natl Acad Sci, doi:10.1073/pnas.0809524106
Bertram, Dijkman, Hajan, Heurich, Gierer et al., TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium, J Virol, doi:10.1128/JVI.03372-12
Bertram, Glowacka, Muller, Lavender, Gnirss et al., Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease, J Virol, doi:10.1128/JVI.05300-11
Bosch, Van Der Zee, De Haan, Rottier, The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex, J Virol, doi:10.1128/jvi.77.16.8801-8811.2003
Chen, Chen, Wen, Ou, Chiou et al., Inhibition of enveloped viruses infectivity by curcumin, PLoS One, doi:10.1371/journal.pone.0062482
Chen, Du, Potential natural compounds for preventing 2019-nCoV infection
Chen, Liu, Guo, Emerging coronaviruses: genome structure, replication, and pathogenesis, J Med Virol, doi:10.1002/jmv.26234
Chowdhury, Sahuc, Rouille, Rivière, Bonneau et al., Polyphenols of black tea, inhibit entry of hepatitis C virus in cell culture, PLoS One, doi:10.1371/journal.pone.0198226
Cory, Passarelli, Szeto, Tamez, Mattei, The Role of polyphenols in human health and food systems: A mini-review, Front Nutr, doi:10.3389/fnut.2018.00087
Coutard, Valle, De Lamballerie, Canard, Seidah et al., The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade, Antiviral Res, doi:10.1016/j.antiviral.2020.104742
Cui, Zhou, Huang, Zhang, Wang et al., Identification of theaflavin-3,3'-digallate as a novel Zika Virus protease inhibitor, Front Pharmacol, doi:10.3389/fphar.2020.514313
Du, He, Zhou, Liu, Zheng et al., The spike protein of SARS-CoV-a target for vaccine and therapeutic development, Nat Rev Microbiol, doi:10.1038/nrmicro2090
Glowacka, Bertram, Muller, Allen, Soilleux et al., Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response, J Virol, doi:10.1128/JVI.02232-10
Goc, Matthias, Niedzwiecki, Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry, Sci. Rep, doi:10.1038/s41598-021-84850-1
Gorbalenya, Baker, Baric, De Groot, Drosten et al., The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2, Nat Microbiol, doi:10.1038/s41564-020-0695-z
Guan, Zheng, He, Liu, Zhuang et al., Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China, Science, doi:10.1126/science.1087139
Hoffmann, Kleine-Weber, Schroeder, Kru ¨ger, Herrler et al., SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell, doi:10.1016/j.cell.2020.02.052
Iwata-Yoshikawa, Okamura, Shimizu, Hasegawa, Takeda et al., TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection, J Virol, doi:10.1128/JVI.01815-18
Jaimes, Andre, Chappie, Jean, Millet et al., Phylogenetic analysis and structural modeling of SARS-CoV-2 spike protein reveals an evolutionary distinct and proteolytically sensitive activation loop, J Mol Biol, doi:10.1016/j.jmb.2020.04.009
Jaruga, Bielak-Zmijewska, Sikora, Skierski, Radziszewska et al., Glutathioneindependent mechanism of apoptosis inhibition by curcumin in rat thymocytes, Biochem Pharmacol, doi:10.1016/s0006-2952%2898%2900144-0
Jena, Kanungo, Nayak, Chainy, Dandapat, Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane: insights from computational study, Sci Rep, doi:10.1038/s41598-021-81462-7
Liu, Luo, Libby, Shi, Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients, Pharmacol Ther
Lung, Lin, Yang, Chou, Chang et al., The potential SARS-CoV-2 entry inhibitor, doi:10.1101/2020.03.26.009803v1
Maiti, Banerjee, Epigallocatechin-gallate and theaflavin-gallate interaction in SARS CoV-2 spike protein central-channel with reference to the hydroxychloroquine interaction. Bioinformatics and molecular docking study, Drug Dev Res, doi:10.1002/ddr.21730
Masters, Perlman, Fields Virology
Mollica, Rizzo, Massari, The pivotal role of TMPRSS2 in coronavirus disease 2019 and prostate cancer, Future Oncol, doi:10.2217/fon-2020-0571
Nelson, Dyall, Hoenen, Barnes, Zhou, The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection, PLoS Negl Trop Dis, doi:10.1371/journal.pntd.0005540
Ohkuma, Poole, Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents, Proc Natl Acad Sci, doi:10.1073/pnas.75.7.3327
Ou, Liu, Lei, Li, Mi et al., Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV, Nat Commun, doi:10.1038/s41467-020-15562-9
Pandey, Rizvi, Plant polyphenols as dietary antioxidants in human health and disease, Oxid Med Cell Longev, doi:10.4161/oxim.2.5.9498
Paraiso, Revel, Stevens, Potential use of polyphenols in the battle against COVID-19, Curr Opin Food Sci, doi:10.1016/j.cofs.2020.08.004
Patel, Rajendran, Shah, Patel, Pakala et al., Virtual screening of curcumin and its analogs against the spike surface glycoprotein of SARS-CoV-2 and SARS-CoV, J Biomol Struct Dyn, doi:10.1080/07391102.2020.1868338
Patil, Saraogi, Natural products as potential drug permeation enhancer in transdermal drug delivery system, Arch Dermatol Res, doi:10.1007/s00403-014-1445-y
Perrotta, Matera, Cazzola, Bianco, Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter?, Respir Med, doi:10.1016/j.rmed.2020.105996
Ravish, Raghav, Curcumin as inhibitor of mammalian cathepsin B, cathepsin H, acid phosphatase and alkaline phosphatase: a correlation with pharmacological activities, Med Chem Res
Rehman, Al-Ajmi, Hussain, Natural compounds as inhibitors of SARS-CoV-2 main protease (3CLpro): A molecular docking and simulation approach to combat COVID-19, Curr Pharm Des, doi:10.2174/1381612826999201116195851
Shrimp, Kales, Sanderson, Simeonov, Shen et al., An enzymatic TMPRSS2 assay for assessment of clinical candidates and discovery of inhibitors as potential treatment of COVID-19, ACS Pharmacol Transl Sci, doi:10.1021/acsptsci.0c00106
Simmons, Gosalia, Rennekamp, Reeves, Diamond et al., Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry, Proc Natl Acad Sci, doi:10.1073/pnas.0505577102
Taggart, Lowe, Greene, Mulgrew, Neill et al., Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor, J Biol Chem, doi:10.1074/jbc.M103220200
Upadhyay, Dixit, Role of polyphenols and other phytochemicals on molecular signaling, Oxid Med Cell Longev, doi:10.1155/2015/504253
Verma, Twilley, Esmear, Oosthuizen, Reid et al., Anti-SARS-CoV natural products with the potential to inhibit SARS-CoV-2 (COVID-19), Front Pharmacol, doi:10.3389/fphar.2020.561334
Wan, Shang, Graham, Baric, Li, Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS, J Virol, doi:10.1128/JVI.00127-20
Wolters, Chapman, Importance of lysosomal cysteine proteases in lung disease, Respir Res, doi:10.1186/rr29
Wu, Liu, Yang, Zhang, Zhong et al., Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharm Sin B, doi:10.1016/j.apsb.2020.02.008
Xia, Lan, Su, Wang, Xu et al., The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin, Signal Transduct Target Ther, doi:10.1038/s41392-020-0184-0
Xu, Chen, Wang, Feng, Zhou et al., Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission, Sci China Life Sci, doi:10.1007/s11427-020-1637-5
Yoo, Lee, Kim, Kang, Park, Curcumin inhibits the upregulation of cathepsin L by palmitate in fat, Endocrine Abstracts
Zhang, Huang, Yang, Liu, Wang et al., Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts, Respir Res, doi:10.1186/1465-9921-12-154
Zhang, Shen, Wang, Cheng, Discovery of anti-SARS-CoV-2 agents from commercially available flavor via docking screening
Zhou, Yang, Wang, Hu, Zhang et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature, doi:10.1038/s41586-020-2012-7
´szti-Gere, Czimmermann, Ujhelyi, Balla, Maiwald et al., In vitro characterization of TMPRSS2 inhibition in IPEC-J2 cells, J Enzyme Inhib Med Chem, doi:10.1080/14756366.2016.1193732
Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop