Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols
et al., Food Chemistry, doi:10.1016/j.foodchem.2021.131594, Nov 2021
Curcumin for COVID-19
16th treatment shown to reduce risk in
February 2021, now with p = 0.0000000061 from 28 studies.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
In silico and in vitro study of plant polyphenols identifying quercetin, curcumin, ellagic acid, epigallocatechin gallate, and resveratrol as SARS-CoV-2 3CLpro inhibitors with IC50 between 11.8µM and 23.4µM. Real-time binding was analyzed with surface plasmon resonance spectroscopy.
59 preclinical studies support the efficacy of curcumin for COVID-19:
In silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spikeA,4,5,10,15,17,23,26 (and specifically the receptor binding domainB,1,3,13,16,19 ), MproC,3-5,10,12,14-16,18,19,21,24,26,27,29,46 , RNA-dependent RNA polymeraseD,3-5,16,25 , PLproE,5, ACE2F,1,17,18,20 , nucleocapsidG,11,28 , nsp10H,28, and helicaseI,34 proteins, and inhibition of spike-ACE2 interactionJ,2.
In vitro studies demonstrate inhibition of the spikeA,39 (and specifically the receptor binding domainB,49), MproC,22,39,46,48 , ACE2F,49, and TMPRSS2K,49 proteins, and inhibition of spike-ACE2 interactionJ,2,32 .
In vitro studies demonstrate efficacy in Calu-3L,47, A549M,39, 293TN,6, HEK293-hACE2O,22,37 , 293T/hACE2/TMPRSS2P,38, Vero E6Q,12,16,26,37,39,41,43,45,47 , and SH-SY5YR,36 cells.
Curcumin decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells45, alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress6, may limit COVID-19 induced cardiac damage by inhibiting the NF-κB signaling pathway which mediates the profibrotic effects of the SARS-CoV-2 spike protein on cardiac fibroblasts33, is predicted to inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain and the human ACE2 receptor for the delta and omicron variants13, lowers ACE2 and STAT3, curbing lung inflammation and ARDS in preclinical COVID-19 models30, inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity40, has direct virucidal action by disrupting viral envelope integrity42, and can function as a photosensitizer in photodynamic therapy to generate reactive oxygen species that damage the virus42.
Study covers curcumin, quercetin, and resveratrol.
1.
Wu et al., Utilizing natural compounds as ligands to disrupt the binding of SARS-CoV-2 receptor-binding domain to angiotensin-converting enzyme 2, impeding viral infection, Phytochemistry Letters, doi:10.1016/j.phytol.2025.102999.
2.
Najimi et al., Phytochemical Inhibitors of SARS‐CoV‐2 Entry: Targeting the ACE2‐RBD Interaction with l‐Tartaric Acid, l‐Ascorbic Acid, and Curcuma longa Extract, ChemistrySelect, doi:10.1002/slct.202406035.
3.
Rajamanickam et al., Exploring the Potential of Siddha Formulation MilagaiKudineer-Derived Phytotherapeutics Against SARS-CoV-2: An In-Silico Investigation for Antiviral Intervention, Journal of Pharmacy and Pharmacology Research, doi:10.26502/fjppr.0105.
4.
Al balawi et al., Assessing multi-target antiviral and antioxidant activities of natural compounds against SARS-CoV-2: an integrated in vitro and in silico study, Bioresources and Bioprocessing, doi:10.1186/s40643-024-00822-z.
5.
Haque et al., Exploring potential therapeutic candidates against COVID-19: a molecular docking study, Discover Molecules, doi:10.1007/s44345-024-00005-5.
6.
Zhang et al., Computational Discovery of Mitochondrial Dysfunction Biomarkers in Severe SARS-CoV-2 Infection: Facilitating Pytomedicine Screening, Phytomedicine, doi:10.1016/j.phymed.2024.155784.
7.
Öztürkkan et al., In Silico investigation of the effects of curcuminoids on the spike protein of the omicron variant of SARS-CoV-2, Baku State University Journal of Chemistry and Material Sciences, 1:2, bsuj.bsu.edu.az/uploads/pdf/ec4204d62f7802de54e6092bf7860029.pdf.
8.
Yunze et al., Therapeutic effect and potential mechanism of curcumin, an active ingredient in Tongnao Decoction, on COVID-19 combined with stroke: a network pharmacology study and GEO database mining, Research Square, doi:10.21203/rs.3.rs-4329762/v1.
9.
Agamah et al., Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases, ScienceOpen, doi:10.58647/DRUGARXIV.PR000010.v1.
10.
Boseila et al., Throat spray formulated with virucidal Pharmaceutical excipients as an effective early prophylactic or treatment strategy against pharyngitis post-exposure to SARS CoV-2, European Journal of Pharmaceutics and Biopharmaceutics, doi:10.1016/j.ejpb.2024.114279.
11.
Hidayah et al., Bioinformatics study of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds in Curcuma longa as an antiviral agent via nucleocapsid on SARS-CoV-2 inhibition, International Conference on Organic and Applied Chemistry, doi:10.1063/5.0197724.
12.
Singh et al., Unlocking the potential of phytochemicals in inhibiting SARS-CoV-2 M Pro protein - An in-silico and cell-based approach, Research Square, doi:10.21203/rs.3.rs-3888947/v1.
13.
Kant et al., Structure-based drug discovery to identify SARS-CoV2 spike protein–ACE2 interaction inhibitors, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2023.2300060.
14.
Naderi Beni et al., In silico studies of anti-oxidative and hot temperament-based phytochemicals as natural inhibitors of SARS-CoV-2 Mpro, PLOS ONE, doi:10.1371/journal.pone.0295014.
15.
Moschovou et al., Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein, International Journal of Molecular Sciences, doi:10.3390/ijms242115894.
16.
Eleraky et al., Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2, International Journal of Nanomedicine, doi:10.2147/IJN.S423251.
17.
Singh (B) et al., Computational studies to analyze effect of curcumin inhibition on coronavirus D614G mutated spike protein, The Seybold Report, doi:10.17605/OSF.IO/TKEXJ.
18.
Thapa et al., In-silico Approach for Predicting the Inhibitory Effect of Home Remedies on Severe Acute Respiratory Syndrome Coronavirus-2, Makara Journal of Science, doi:10.7454/mss.v27i3.1609.
19.
Srivastava et al., Paradigm of Well-Orchestrated Pharmacokinetic Properties of Curcuminoids Relative to Conventional Drugs for the Inactivation of SARS-CoV-2 Receptors: An In Silico Approach, Stresses, doi:10.3390/stresses3030043.
20.
Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.
21.
Winih Kinasih et al., Analisis in silico interaksi senyawa kurkuminoid terhadap enzim main protease 6LU7 dari SARS-CoV-2, Duta Pharma Journal, doi:10.47701/djp.v3i1.2904.
22.
Wu (B) et al., Potential Mechanism of Curcumin and Resveratrol against SARS-CoV-2, Research Square, doi:10.21203/rs.3.rs-2780614/v1.
23.
Nag et al., Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study, Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2022.105552.
24.
Rampogu et al., Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2, International Journal of Molecular Sciences, doi:10.3390/ijms23031771.
25.
Singh (C) et al., Potential of turmeric-derived compounds against RNA-dependent RNA polymerase of SARS-CoV-2: An in-silico approach, Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2021.104965.
26.
Kandeil et al., Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2, Pathogens, doi:10.3390/pathogens10060758.
27.
Rajagopal et al., Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach, Future Journal of Pharmaceutical Sciences, doi:10.1186/s43094-020-00126-x.
28.
Suravajhala et al., Comparative Docking Studies on Curcumin with COVID-19 Proteins, Preprints, doi:10.20944/preprints202005.0439.v3.
29.
Sekiou et al., In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine Against COVID-19 Main Protease Active Site and ACE2, ChemRxiv, doi:10.26434/chemrxiv.12181404.v1.
30.
Aktay et al., Oral Administration of Water-Soluble Curcumin Complex Prevents ARDS With the Potential for COVID-19 Treatment, Phytotherapy Research, doi:10.1002/ptr.70046.
31.
Olubiyi et al., Novel dietary herbal preparations with inhibitory activities against multiple SARS-CoV-2 targets: A multidisciplinary investigation into antiviral activities, Food Chemistry Advances, doi:10.1016/j.focha.2025.100969.
32.
Emam et al., Establishment of in-house assay for screening of anti-SARS-CoV-2 protein inhibitors, AMB Express, doi:10.1186/s13568-024-01739-8.
33.
Van Tin et al., Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3 Inflammasomes and NF-κB Signaling, Cells, doi:10.3390/cells13161331.
34.
Li et al., Thermal shift assay (TSA)-based drug screening strategy for rapid discovery of inhibitors against the Nsp13 helicase of SARS-CoV-2, Animals and Zoonoses, doi:10.1016/j.azn.2024.06.001.
35.
Kamble et al., Nanoparticulate curcumin spray imparts prophylactic and therapeutic properties against SARS-CoV-2, Emergent Materials, doi:10.1007/s42247-024-00754-6.
36.
Nicoliche et al., Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2, Scientific Reports, doi:10.1038/s41598-024-61662-7.
37.
Nittayananta et al., A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity, Virology Journal, doi:10.1186/s12985-023-02282-x.
38.
Septisetyani et al., Curcumin and turmeric extract inhibited SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion, bioRxiv, doi:10.1101/2023.09.28.560070.
39.
Mohd Abd Razak et al., In Vitro Anti-SARS-CoV-2 Activities of Curcumin and Selected Phenolic Compounds, Natural Product Communications, doi:10.1177/1934578X231188861.
40.
Fam et al., Channel activity of SARS-CoV-2 viroporin ORF3a inhibited by adamantanes and phenolic plant metabolites, Scientific Reports, doi:10.1038/s41598-023-31764-9.
41.
Teshima et al., Antiviral activity of curcumin and its analogs selected by an artificial intelligence-supported activity prediction system in SARS-CoV-2-infected VeroE6 cells, Natural Product Research, doi:10.1080/14786419.2023.2194647.
42.
Zupin et al., Optimization of Anti-SARS-CoV-2 Treatments Based on Curcumin, Used Alone or Employed as a Photosensitizer, Viruses, doi:10.3390/v14102132.
43.
Leka et al., In vitro antiviral activity against SARS-CoV-2 of common herbal medicinal extracts and their bioactive compounds, Phytotherapy Research, doi:10.1002/ptr.7463.
44.
Goc et al., Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants, European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022.
45.
Marín-Palma et al., Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms, Molecules, doi:10.3390/molecules26226900.
46.
Bahun et al., Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols, Food Chemistry, doi:10.1016/j.foodchem.2021.131594.
47.
Bormann et al., Turmeric Root and Its Bioactive Ingredient Curcumin Effectively Neutralize SARS-CoV-2 In Vitro, Viruses, doi:10.3390/v13101914.
a.
The trimeric spike (S) protein is a glycoprotein that mediates viral entry by binding to the host ACE2 receptor, is critical for SARS-CoV-2's ability to infect host cells, and is a target of neutralizing antibodies. Inhibition of the spike protein prevents viral attachment, halting infection at the earliest stage.
b.
The receptor binding domain is a specific region of the spike protein that binds ACE2 and is a major target of neutralizing antibodies. Focusing on the precise binding site allows highly specific disruption of viral attachment with reduced potential for off-target effects.
c.
The main protease or Mpro, also known as 3CLpro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting Mpro disrupts the SARS-CoV-2 lifecycle within the host cell, preventing the creation of new copies.
d.
RNA-dependent RNA polymerase (RdRp), also called nsp12, is the core enzyme of the viral replicase-transcriptase complex that copies the positive-sense viral RNA genome into negative-sense templates for progeny RNA synthesis. Inhibiting RdRp blocks viral genome replication and transcription.
e.
The papain-like protease (PLpro) has multiple functions including cleaving viral polyproteins and suppressing the host immune response by deubiquitination and deISGylation of host proteins. Inhibiting PLpro may block viral replication and help restore normal immune responses.
f.
The angiotensin converting enzyme 2 (ACE2) protein is a host cell transmembrane protein that serves as the cellular receptor for the SARS-CoV-2 spike protein. ACE2 is expressed on many cell types, including epithelial cells in the lungs, and allows the virus to enter and infect host cells. Inhibition may affect ACE2's physiological function in blood pressure control.
g.
The nucleocapsid (N) protein binds and encapsulates the viral genome by coating the viral RNA. N enables formation and release of infectious virions and plays additional roles in viral replication and pathogenesis. N is also an immunodominant antigen used in diagnostic assays.
h.
Non-structural protein 10 (nsp10) serves as an RNA chaperone and stabilizes conformations of nsp12 and nsp14 in the replicase-transcriptase complex, which synthesizes new viral RNAs. Nsp10 disruption may destabilize replicase-transcriptase complex activity.
i.
The helicase, or nsp13, protein unwinds the double-stranded viral RNA, a crucial step in replication and transcription. Inhibition may prevent viral genome replication and the creation of new virus components.
j.
The interaction between the SARS-CoV-2 spike protein and the human ACE2 receptor is a primary method of viral entry, inhibiting this interaction can prevent the virus from attaching to and entering host cells, halting infection at an early stage.
k.
Transmembrane protease serine 2 (TMPRSS2) is a host cell protease that primes the spike protein, facilitating cellular entry. TMPRSS2 activity helps enable cleavage of the spike protein required for membrane fusion and virus entry. Inhibition may especially protect respiratory epithelial cells, buy may have physiological effects.
l.
Calu-3 is a human lung adenocarcinoma cell line with moderate ACE2 and TMPRSS2 expression and SARS-CoV-2 susceptibility. It provides a model of the human respiratory epithelium, but many not be ideal for modeling early stages of infection due to the moderate expression levels of ACE2 and TMPRSS2.
m.
A549 is a human lung carcinoma cell line with low ACE2 expression and SARS-CoV-2 susceptibility. Viral entry/replication can be studied but the cells may not replicate all aspects of lung infection.
n.
293T is a human embryonic kidney cell line that can be engineered for high ACE2 expression and SARS-CoV-2 susceptibility. 293T cells are easily transfected and support high protein expression.
o.
HEK293-hACE2 is a human embryonic kidney cell line with high ACE2 expression and SARS-CoV-2 susceptibility. Cells have been transfected with a plasmid to express the human ACE2 (hACE2) protein.
p.
293T/hACE2/TMPRSS2 is a human embryonic kidney cell line engineered for high ACE2 and TMPRSS2 expression, which mimics key aspects of human infection. 293T/hACE2/TMPRSS2 cells are very susceptible to SARS-CoV-2 infection.
q.
Vero E6 is an African green monkey kidney cell line with low/no ACE2 expression and high SARS-CoV-2 susceptibility. The cell line is easy to maintain and supports robust viral replication, however the monkey origin may not accurately represent human responses.
r.
SH-SY5Y is a human neuroblastoma cell line that exhibits neuronal phenotypes. It is commonly used as an in vitro model for studying neurotoxicity, neurodegenerative diseases, and neuronal differentiation.
Bahun et al., 14 Nov 2021, peer-reviewed, 10 authors.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols
Food Chemistry, doi:10.1016/j.foodchem.2021.131594
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Conflicts of interest: The authors declare that they have no conflicts of interest. Appendix A. Supplementary material
References
Abbas, Saeed, Anjum, Afzaal, Tufail et al., Natural polyphenols: an overview, International Journal of Food Properties, doi:10.1080/10942912.2016.1220393
Abian, Ortega-Alarcon, Jimenez-Alesanco, Ceballos-Laita, Vega et al., Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening, International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2020.07.235
Baell, Holloway, New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays, Journal of Medicinal Chemistry, doi:10.1021/jm901137j
Calland, Sahuc, Belouzard, Bonnafous, Mesalam et al., Polyphenols inhibit hepatitis C virus entry by a new mechanism of action, Journal of Virology, doi:10.1128/JVI.01473-15
Campagna, Rivas, Antiviral activity of resveratrol, Biochemical Society Transactions, doi:10.1042/BST0380050
Chiou, Chen, Chen, Yang, Hwang et al., The inhibitory effects of PGG and EGCG against the SARS-CoV-2 3C-like protease, Biochemical and Biophysical Research Communications, doi:10.1016/j.bbrc.2020.12.106
Dai, Zhang, Jiang, Su, Li et al., Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease, Science, doi:10.1126/science.abb4489
Daniel, Krupnick, Heur, Blinzler, Nims et al., Extraction, stability, and quantitation of ellagic acid in various fruits and nuts, Journal of Food Composition and Analysis, doi:10.1016/0889-1575(89)90005-7
Dewit, Van Doremalen, Falzarano, Munster, SARS and MERS: recent insights into emerging coronaviruses, Nature Reviews Microbiology, doi:10.1038/nrmicro.2016.81
Du, Zheng, Disoma, Li, Chen et al., Epigallocatechin-3-gallate, an active ingredient of traditional Chinese medicines, inhibits the 3CL pro activity of SARS-CoV-2, International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2021.02.012
El-Missiry, Fekri, Kesar, Othman, Polyphenols are potential nutritional adjuvants for targeting COVID-19, Phytotherapy Research, doi:10.1002/ptr.6992
Friesner, Murphy, Repasky, Frye, Greenwood et al., Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein−ligand complexes, Journal of Medicinal Chemistry, doi:10.1021/jm051256o
Fry, Cai, Zhang, Wagner, Consolidation in a crisis: patterns of international collaboration in early COVID-19 research, PLoS ONE, doi:10.1371/journal.pone.0236307
Goc, Sumera, Rath, Niedzwiecki, Phenolic compounds disrupt Spike-mediated receptor binding and entry of SARS-CoV-2, PLoS ONE, doi:10.1371/journal.pone.0253489
Houston, Walkinshaw, Consensus docking: improving the reliability of docking in a virtual screening context, Journal of Chemical Information and Modeling, doi:10.1021/ci300399w
Huynh, Wang, Luan, In-silico exploration of the molecular mechanism of clinically oriented drugs for possibly inhibiting SARS-CoV-2 main protease, Journal of Physical Chemistry Letters, doi:10.1021/acs.jpclett.0c00994
Kahn, Mcintosh, History and recent advances in coronavirus discovery, The Pediatric Infectious Disease Journal
Khalifa, Zhu, Mohammed, Dutta, Li, Tannins inhibit SARS-CoV-2 through binding with catalytic dyad residues of 3CL pro : an in-silico approach with 19 structural different hydrolysable tannins, Journal of Food Biochemistry, doi:10.1111/jfbc.13432
Khan, Heng, Wang, Qiu, Wei et al., In silico and in vitro evaluation of kaempferol as a potential inhibitor of the SARS-CoV-2 main protease (3CLpro), Phytotherapy Research, doi:10.1002/ptr.6998
Khan, Umbreen, Hameed, Fatima, Zahoor et al., In Silico Mutagenesis-Based Remodelling of SARS-CoV-1 Peptide (ATLQAIAS) to Inhibit SARS-CoV-2: Structural-Dynamics and Free Energy Calculations, Interdisciplinary Sciences: Computational Life Sciences, doi:10.1007/s12539-021-00447-2
Kim, Narayanan, Chang, Inhibition of influenza virus replication by plant-derived isoquercetin, Antiviral Research, doi:10.1016/j.antiviral.2010.08.016
Krieger, Vriend, New ways to boost molecular dynamics simulations, Journal of Computational Chemistry, doi:10.1002/jcc.23899
Mathew, Hsu, Antiviral potential of curcumin, Journal of Functional Foods, doi:10.1016/j.jff.2017.12.017
Mehany, Khalifa, Barakat, Althwab, Alharbi et al., Polyphenols as promising biologically active substances for preventing SARS-CoV-2: a review with research evidence and underlying mechanisms, Food Bioscience, doi:10.1016/j.fbio.2021.100891
Mody, Ho, Wills, Mawri, Lawson et al., Identification of 3-chymotrypsin like protease (3CL pro ) inhibitors as potential anti-SARS-CoV-2 agents, Communications Biology, doi:10.1038/s42003-020-01577-x
Ni, Chen, Wei, Lan, Qiu et al., Study on the mechanism of active components of Liupao tea on 3CL pro based on HPLC-DAD fingerprint and molecular docking technique, Journal of Food Biochemistry, doi:10.1111/jfbc.13707
Paraiso, Revel, Stevens, Potential use of polyphenols in the battle against COVID-19, Current Opinion in Food Science, doi:10.1016/j.cofs.2020.08.004
Pasquereau, Nehme, Ahmad, Daouad, Van Assche et al., Resveratrol inhibits HCoV-229E and SARS-CoV-2 coronavirus replication in vitro, Viruses, doi:10.3390/v13020354
Rasouli, Farzaei, Khodarahmi, Polyphenols and their benefits: a review, International Journal of Food Properties, doi:10.1080/10942912.2017.1354017
Rizzuti, Grande, Conforti, Jimenez-Alesanco, Ceballos-Laita et al., Rutin Is a low micromolar inhibitor of SARS-CoV-2 main protease 3CL pro : implications for drug design of quercetin analogs, Biomedicines, doi:10.3390/biomedicines9040375
Ruiz-Carmona, Alvarez-Garcia, Foloppe, Garmendia-Doval, Juhos, rDock: a fast, versatile and open source program for docking ligands to proteins and nucleic acids, PLoS Computational Biology, doi:10.1371/journal.pcbi.1003571
Ryu, Park, Kim, Lee, Seo et al., SARS-CoV 3CL pro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii, Bioorganic and Medicinal Chemistry Letters, doi:10.1016/j.bmcl.2010.01.152
Sarkar, Mondal, Torequl Islam, Martorell, Docea et al., Potential therapeutic options for COVID-19: current status, challenges, and future perspectives, Frontiers in Pharmacology, doi:10.3389/fphar.2020.572870
Treutter, Significance of flavonoids in plant resistance: a review, Environmental Chemistry Letters, doi:10.1007/s10311-006-0068-8
Trott, Olson, AutoDock VINA: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, Journal of Computational Chemistry, doi:10.1002/jcc.21334
Wang, Horby, Hayden, Gao, A novel coronavirus outbreak of global health concern, The Lancet, doi:10.1016/S0140-6736(20)30185-9
Williamson, The role of polyphenols in modern nutrition, Nutrition Bulletin, doi:10.1111/nbu.12278
Yang, Wei, Huang, Lei, Shen et al., Resveratrol inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cultured Vero cells, Phytotherapy Research, doi:10.1002/ptr.6916
Yang, Yu, Huang, Swine enteric alphacoronavirus (swine acute diarrhea syndrome coronavirus): an update three years after its discovery, Virus Research, doi:10.1016/j.virusres.2020.198024
Zhu, Zhang, Wang, Li, Yang et al., A novel coronavirus from patients with pneumonia in China, 2019, New England Journal of Medicine, doi:10.1056/NEJMoa2001017
DOI record:
{
"DOI": "10.1016/j.foodchem.2021.131594",
"ISSN": [
"0308-8146"
],
"URL": "http://dx.doi.org/10.1016/j.foodchem.2021.131594",
"alternative-id": [
"S0308814621026005"
],
"article-number": "131594",
"assertion": [
{
"label": "This article is maintained by",
"name": "publisher",
"value": "Elsevier"
},
{
"label": "Article Title",
"name": "articletitle",
"value": "Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols"
},
{
"label": "Journal Title",
"name": "journaltitle",
"value": "Food Chemistry"
},
{
"label": "CrossRef DOI link to publisher maintained version",
"name": "articlelink",
"value": "https://doi.org/10.1016/j.foodchem.2021.131594"
},
{
"label": "Content Type",
"name": "content_type",
"value": "article"
},
{
"label": "Copyright",
"name": "copyright",
"value": "© 2021 The Authors. Published by Elsevier Ltd."
}
],
"author": [
{
"affiliation": [],
"family": "Bahun",
"given": "Miha",
"sequence": "first"
},
{
"affiliation": [],
"family": "Jukić",
"given": "Marko",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Oblak",
"given": "Domen",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Kranjc",
"given": "Luka",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Bajc",
"given": "Gregor",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Butala",
"given": "Matej",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Bozovičar",
"given": "Krištof",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Bratkovič",
"given": "Tomaž",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Podlipnik",
"given": "Črtomir",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Poklar Ulrih",
"given": "Nataša",
"sequence": "additional"
}
],
"container-title": "Food Chemistry",
"container-title-short": "Food Chemistry",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"elsevier.com",
"sciencedirect.com"
]
},
"created": {
"date-parts": [
[
2021,
11,
14
]
],
"date-time": "2021-11-14T14:52:17Z",
"timestamp": 1636901537000
},
"deposited": {
"date-parts": [
[
2023,
11,
12
]
],
"date-time": "2023-11-12T16:18:36Z",
"timestamp": 1699805916000
},
"funder": [
{
"DOI": "10.13039/501100004329",
"award": [
"P4-0121"
],
"doi-asserted-by": "publisher",
"name": "Javna Agencija za Raziskovalno Dejavnost RS"
},
{
"DOI": "10.13039/501100005989",
"award": [
"OP20.04342"
],
"doi-asserted-by": "publisher",
"name": "Ministrstvo za Izobraževanje, Znanost in Šport"
}
],
"indexed": {
"date-parts": [
[
2024,
1,
1
]
],
"date-time": "2024-01-01T18:29:16Z",
"timestamp": 1704133756503
},
"is-referenced-by-count": 57,
"issued": {
"date-parts": [
[
2022,
3
]
]
},
"language": "en",
"license": [
{
"URL": "https://www.elsevier.com/tdm/userlicense/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2022,
3,
1
]
],
"date-time": "2022-03-01T00:00:00Z",
"timestamp": 1646092800000
}
},
{
"URL": "http://creativecommons.org/licenses/by/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2021,
11,
14
]
],
"date-time": "2021-11-14T00:00:00Z",
"timestamp": 1636848000000
}
}
],
"link": [
{
"URL": "https://api.elsevier.com/content/article/PII:S0308814621026005?httpAccept=text/xml",
"content-type": "text/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://api.elsevier.com/content/article/PII:S0308814621026005?httpAccept=text/plain",
"content-type": "text/plain",
"content-version": "vor",
"intended-application": "text-mining"
}
],
"member": "78",
"original-title": [],
"page": "131594",
"prefix": "10.1016",
"published": {
"date-parts": [
[
2022,
3
]
]
},
"published-print": {
"date-parts": [
[
2022,
3
]
]
},
"publisher": "Elsevier BV",
"reference": [
{
"DOI": "10.1080/10942912.2016.1220393",
"article-title": "Natural polyphenols: An overview",
"author": "Abbas",
"doi-asserted-by": "crossref",
"first-page": "1689",
"issue": "8",
"journal-title": "International Journal of Food Properties",
"key": "10.1016/j.foodchem.2021.131594_b0005",
"volume": "20",
"year": "2017"
},
{
"DOI": "10.1016/j.ijbiomac.2020.07.235",
"article-title": "Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening",
"author": "Abian",
"doi-asserted-by": "crossref",
"first-page": "1693",
"journal-title": "International Journal of Biological Macromolecules",
"key": "10.1016/j.foodchem.2021.131594_b0010",
"volume": "164",
"year": "2020"
},
{
"DOI": "10.1021/jm901137j",
"article-title": "New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays",
"author": "Baell",
"doi-asserted-by": "crossref",
"first-page": "2719",
"issue": "7",
"journal-title": "Journal of Medicinal Chemistry",
"key": "10.1016/j.foodchem.2021.131594_b0015",
"volume": "53",
"year": "2010"
},
{
"DOI": "10.1128/JVI.01473-15",
"article-title": "Polyphenols inhibit hepatitis C virus entry by a new mechanism of action",
"author": "Calland",
"doi-asserted-by": "crossref",
"first-page": "10053",
"issue": "19",
"journal-title": "Journal of Virology",
"key": "10.1016/j.foodchem.2021.131594_b0020",
"volume": "89",
"year": "2015"
},
{
"DOI": "10.1042/BST0380050",
"article-title": "Antiviral activity of resveratrol",
"author": "Campagna",
"doi-asserted-by": "crossref",
"first-page": "50",
"issue": "1",
"journal-title": "Biochemical Society Transactions",
"key": "10.1016/j.foodchem.2021.131594_b0025",
"volume": "38",
"year": "2010"
},
{
"article-title": "The inhibitory effects of PGG and EGCG against the SARS-CoV-2 3C-like protease",
"author": "Chiou",
"journal-title": "Biochemical and Biophysical Research Communications.",
"key": "10.1016/j.foodchem.2021.131594_b0030",
"year": "2021"
},
{
"DOI": "10.1126/science.abb4489",
"article-title": "Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease",
"author": "Dai",
"doi-asserted-by": "crossref",
"first-page": "1331",
"issue": "6497",
"journal-title": "Science",
"key": "10.1016/j.foodchem.2021.131594_b0035",
"volume": "368",
"year": "2020"
},
{
"DOI": "10.1016/0889-1575(89)90005-7",
"article-title": "Extraction, stability, and quantitation of ellagic acid in various fruits and nuts",
"author": "Daniel",
"doi-asserted-by": "crossref",
"first-page": "338",
"issue": "4",
"journal-title": "Journal of Food Composition and Analysis",
"key": "10.1016/j.foodchem.2021.131594_b0040",
"volume": "2",
"year": "1989"
},
{
"DOI": "10.1038/nrmicro.2016.81",
"article-title": "SARS and MERS: Recent insights into emerging coronaviruses",
"author": "de Wit",
"doi-asserted-by": "crossref",
"first-page": "523",
"issue": "8",
"journal-title": "Nature Reviews Microbiology",
"key": "10.1016/j.foodchem.2021.131594_b0045",
"volume": "14",
"year": "2016"
},
{
"DOI": "10.1016/j.ijbiomac.2021.02.012",
"article-title": "Epigallocatechin-3-gallate, an active ingredient of traditional Chinese medicines, inhibits the 3CLpro activity of SARS-CoV-2",
"author": "Du",
"doi-asserted-by": "crossref",
"first-page": "1",
"journal-title": "International Journal of Biological Macromolecules",
"key": "10.1016/j.foodchem.2021.131594_b0050",
"volume": "176",
"year": "2021"
},
{
"DOI": "10.1002/ptr.6992",
"article-title": "Polyphenols are potential nutritional adjuvants for targeting COVID-19",
"author": "El-Missiry",
"doi-asserted-by": "crossref",
"first-page": "2879",
"issue": "6",
"journal-title": "Phytotherapy Research",
"key": "10.1016/j.foodchem.2021.131594_b0055",
"volume": "35",
"year": "2021"
},
{
"DOI": "10.1021/jm051256o",
"article-title": "Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein−ligand complexes",
"author": "Friesner",
"doi-asserted-by": "crossref",
"first-page": "6177",
"issue": "21",
"journal-title": "Journal of Medicinal Chemistry",
"key": "10.1016/j.foodchem.2021.131594_b0060",
"volume": "49",
"year": "2006"
},
{
"DOI": "10.1371/journal.pone.0236307",
"article-title": "Consolidation in a crisis: Patterns of international collaboration in early COVID-19 research",
"author": "Fry",
"doi-asserted-by": "crossref",
"first-page": "e0236307",
"issue": "7",
"journal-title": "PLoS ONE",
"key": "10.1016/j.foodchem.2021.131594_b0065",
"volume": "15",
"year": "2020"
},
{
"DOI": "10.1371/journal.pone.0253489",
"article-title": "Phenolic compounds disrupt Spike-mediated receptor binding and entry of SARS-CoV-2",
"author": "Goc",
"doi-asserted-by": "crossref",
"issue": "6",
"journal-title": "PLoS ONE",
"key": "10.1016/j.foodchem.2021.131594_b0070",
"volume": "16",
"year": "2021"
},
{
"DOI": "10.1021/ci300399w",
"article-title": "Consensus docking: Improving the reliability of docking in a virtual screening context",
"author": "Houston",
"doi-asserted-by": "crossref",
"first-page": "384",
"issue": "2",
"journal-title": "Journal of Chemical Information and Modeling",
"key": "10.1016/j.foodchem.2021.131594_b0075",
"volume": "53",
"year": "2013"
},
{
"DOI": "10.1021/acs.jpclett.0c00994",
"article-title": "In-silico exploration of the molecular mechanism of clinically oriented drugs for possibly inhibiting SARS-CoV-2 main protease",
"author": "Huynh",
"doi-asserted-by": "crossref",
"first-page": "4413",
"issue": "11",
"journal-title": "Journal of Physical Chemistry Letters",
"key": "10.1016/j.foodchem.2021.131594_b0080",
"volume": "11",
"year": "2020"
},
{
"article-title": "In silico and in vitro evaluation of kaempferol as a potential inhibitor of the SARS-CoV-2 main protease (3CLpro)",
"author": "Khan",
"journal-title": "Phytotherapy Research",
"key": "10.1016/j.foodchem.2021.131594_b0085",
"volume": "1–5",
"year": "2021"
},
{
"article-title": "In silico mutagenesis-based remodelling of SARS-CoV-1 peptide (ATLQAIAS) to inhibit SARS-CoV-2: structural-dynamics and free energy calculations",
"author": "Khan",
"first-page": "521",
"issue": "3",
"journal-title": "Interdisciplinary Sciences: Computational Life Sciences",
"key": "10.1016/j.foodchem.2021.131594_b0090",
"volume": "13",
"year": "2021"
},
{
"DOI": "10.1097/01.inf.0000188166.17324.60",
"article-title": "History and recent advances in coronavirus discovery",
"author": "Kahn",
"doi-asserted-by": "crossref",
"first-page": "S223",
"issue": "11",
"journal-title": "The Pediatric Infectious Disease Journal",
"key": "10.1016/j.foodchem.2021.131594_b0095",
"volume": "24",
"year": "2005"
},
{
"DOI": "10.1111/jfbc.13432",
"article-title": "Tannins inhibit SARS-CoV-2 through binding with catalytic dyad residues of 3CLpro: An in-silico approach with 19 structural different hydrolysable tannins",
"author": "Khalifa",
"doi-asserted-by": "crossref",
"issue": "10",
"journal-title": "Journal of Food Biochemistry",
"key": "10.1016/j.foodchem.2021.131594_b0100",
"volume": "44",
"year": "2020"
},
{
"DOI": "10.1016/j.antiviral.2010.08.016",
"article-title": "Inhibition of influenza virus replication by plant-derived isoquercetin",
"author": "Kim",
"doi-asserted-by": "crossref",
"first-page": "227",
"issue": "2",
"journal-title": "Antiviral Research",
"key": "10.1016/j.foodchem.2021.131594_b0105",
"volume": "88",
"year": "2010"
},
{
"DOI": "10.1002/jcc.23899",
"article-title": "New ways to boost molecular dynamics simulations",
"author": "Krieger",
"doi-asserted-by": "crossref",
"first-page": "996",
"issue": "13",
"journal-title": "Journal of Computational Chemistry",
"key": "10.1016/j.foodchem.2021.131594_b0110",
"volume": "36",
"year": "2015"
},
{
"DOI": "10.1016/j.jff.2017.12.017",
"article-title": "Antiviral potential of curcumin",
"author": "Mathew",
"doi-asserted-by": "crossref",
"first-page": "692",
"journal-title": "Journal of Functional Foods",
"key": "10.1016/j.foodchem.2021.131594_b0115",
"volume": "40",
"year": "2018"
},
{
"DOI": "10.1016/j.fbio.2021.100891",
"article-title": "Polyphenols as promising biologically active substances for preventing SARS-CoV-2: A review with research evidence and underlying mechanisms",
"author": "Mehany",
"doi-asserted-by": "crossref",
"first-page": "100891",
"journal-title": "Food Bioscience",
"key": "10.1016/j.foodchem.2021.131594_b0120",
"volume": "40",
"year": "2021"
},
{
"DOI": "10.1038/s42003-020-01577-x",
"article-title": "Identification of 3-chymotrypsin like protease (3CLpro) inhibitors as potential anti-SARS-CoV-2 agents",
"author": "Mody",
"doi-asserted-by": "crossref",
"issue": "1",
"journal-title": "Communications Biology",
"key": "10.1016/j.foodchem.2021.131594_b0125",
"volume": "4",
"year": "2021"
},
{
"DOI": "10.1111/jfbc.13707",
"article-title": "Study on the mechanism of active components of Liupao tea on 3CLpro based on HPLC-DAD fingerprint and molecular docking technique",
"author": "Ni",
"doi-asserted-by": "crossref",
"issue": "5",
"journal-title": "Journal of Food Biochemistry",
"key": "10.1016/j.foodchem.2021.131594_b0130",
"volume": "45",
"year": "2021"
},
{
"DOI": "10.1016/j.cofs.2020.08.004",
"article-title": "Potential use of polyphenols in the battle against COVID-19",
"author": "Paraiso",
"doi-asserted-by": "crossref",
"first-page": "149",
"journal-title": "Current Opinion in Food Science",
"key": "10.1016/j.foodchem.2021.131594_b0135",
"volume": "32",
"year": "2020"
},
{
"DOI": "10.3390/v13020354",
"article-title": "Resveratrol inhibits HCoV-229E and SARS-CoV-2 coronavirus replication in vitro",
"author": "Pasquereau",
"doi-asserted-by": "crossref",
"first-page": "354",
"issue": "2",
"journal-title": "Viruses",
"key": "10.1016/j.foodchem.2021.131594_b0140",
"volume": "13",
"year": "2021"
},
{
"article-title": "Polyphenols and their benefits: A review",
"author": "Rasouli",
"first-page": "1700",
"issue": "2",
"journal-title": "International Journal of Food Properties",
"key": "10.1016/j.foodchem.2021.131594_b0145",
"volume": "20",
"year": "2017"
},
{
"DOI": "10.3390/biomedicines9040375",
"article-title": "Rutin Is a low micromolar inhibitor of SARS-CoV-2 main protease 3CLpro: Implications for drug design of quercetin analogs",
"author": "Rizzuti",
"doi-asserted-by": "crossref",
"first-page": "375",
"issue": "4",
"journal-title": "Biomedicines",
"key": "10.1016/j.foodchem.2021.131594_b0150",
"volume": "9",
"year": "2021"
},
{
"DOI": "10.1371/journal.pcbi.1003571",
"article-title": "rDock: A fast, versatile and open source program for docking ligands to proteins and nucleic acids",
"author": "Ruiz-Carmona",
"doi-asserted-by": "crossref",
"first-page": "e1003571",
"issue": "4",
"journal-title": "PLoS Computational Biology",
"key": "10.1016/j.foodchem.2021.131594_b0155",
"volume": "10",
"year": "2014"
},
{
"DOI": "10.1016/j.bmcl.2010.01.152",
"article-title": "SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii",
"author": "Ryu",
"doi-asserted-by": "crossref",
"first-page": "1873",
"issue": "6",
"journal-title": "Bioorganic and Medicinal Chemistry Letters",
"key": "10.1016/j.foodchem.2021.131594_b0160",
"volume": "20",
"year": "2010"
},
{
"DOI": "10.3389/fphar.2020.572870",
"article-title": "Potential therapeutic options for COVID-19: Current status, challenges, and future perspectives",
"author": "Sarkar",
"doi-asserted-by": "crossref",
"journal-title": "Frontiers in Pharmacology",
"key": "10.1016/j.foodchem.2021.131594_b0165",
"volume": "11",
"year": "2020"
},
{
"DOI": "10.1007/s10311-006-0068-8",
"article-title": "Significance of flavonoids in plant resistance: A review",
"author": "Treutter",
"doi-asserted-by": "crossref",
"first-page": "147",
"issue": "3",
"journal-title": "Environmental Chemistry Letters",
"key": "10.1016/j.foodchem.2021.131594_b0170",
"volume": "4",
"year": "2006"
},
{
"DOI": "10.1002/jcc.21334",
"article-title": "AutoDock VINA: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading",
"author": "Trott",
"doi-asserted-by": "crossref",
"first-page": "455",
"issue": "2",
"journal-title": "Journal of Computational Chemistry",
"key": "10.1016/j.foodchem.2021.131594_b0175",
"volume": "31",
"year": "2010"
},
{
"DOI": "10.1016/S0140-6736(20)30185-9",
"article-title": "A novel coronavirus outbreak of global health concern",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "470",
"issue": "10223",
"journal-title": "The Lancet",
"key": "10.1016/j.foodchem.2021.131594_b0180",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1111/nbu.12278",
"article-title": "The role of polyphenols in modern nutrition",
"author": "Williamson",
"doi-asserted-by": "crossref",
"first-page": "226",
"issue": "3",
"journal-title": "Nutrition Bulletin",
"key": "10.1016/j.foodchem.2021.131594_b0185",
"volume": "42",
"year": "2017"
},
{
"DOI": "10.1002/ptr.6916",
"article-title": "Resveratrol inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cultured Vero cells",
"author": "Yang",
"doi-asserted-by": "crossref",
"first-page": "1127",
"issue": "3",
"journal-title": "Phytotherapy Research",
"key": "10.1016/j.foodchem.2021.131594_b0190",
"volume": "35",
"year": "2020"
},
{
"DOI": "10.1016/j.virusres.2020.198024",
"article-title": "Swine enteric alphacoronavirus (swine acute diarrhea syndrome coronavirus): An update three years after its discovery",
"author": "Yang",
"doi-asserted-by": "crossref",
"first-page": "198024",
"journal-title": "Virus Research",
"key": "10.1016/j.foodchem.2021.131594_b0195",
"volume": "285",
"year": "2020"
},
{
"DOI": "10.1056/NEJMoa2001017",
"article-title": "A novel coronavirus from patients with pneumonia in China, 2019",
"author": "Zhu",
"doi-asserted-by": "crossref",
"first-page": "727",
"issue": "8",
"journal-title": "New England Journal of Medicine",
"key": "10.1016/j.foodchem.2021.131594_b0200",
"volume": "382",
"year": "2020"
}
],
"reference-count": 40,
"references-count": 40,
"relation": {},
"resource": {
"primary": {
"URL": "https://linkinghub.elsevier.com/retrieve/pii/S0308814621026005"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [
"General Medicine",
"Food Science",
"Analytical Chemistry"
],
"subtitle": [],
"title": "Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols",
"type": "journal-article",
"update-policy": "http://dx.doi.org/10.1016/elsevier_cm_policy",
"volume": "373"
}