Analgesics⏵
Antiandrogens⏵
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle⏵
Melatonin
Metformin
Minerals⏵
Molnupiravir
Monoclonals⏵
Naso/orophar..⏵
Nigella Sativa
Nitazoxanide
PPIs
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins⏵
More⏵

Other
Feedback
Home
Top
Abstract
All quercetin studies
Meta analysis
 
Feedback
Home
←
next
study
→
previous
study
c19early.org COVID-19 treatment researchQuercetinQuercetin (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta PPIs Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta
Home Adoption Other Treatments
@CovidAnalysis
All Studies   Meta Analysis    Recent:   

Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics

Waqas et al., Current Medicinal Chemistry, doi:10.2174/0109298673292839240329081008
Apr 2024  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Quercetin for COVID-19
23rd treatment shown to reduce risk in July 2021
 
*, now with p = 0.0031 from 11 studies.
Lower risk for ICU admission, hospitalization, recovery, cases, and viral clearance.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,500+ studies for 81 treatments. c19early.org
In Silico and In Vitro study showing potential inhibition of SARS-CoV-2 main protease (Mpro) by quercetin and four other natural compounds isolated from medicinal plants. Authors used molecular docking, molecular dynamics simulations, and in vitro enzyme inhibition assays to assess the compounds' binding affinity and inhibitory activity against Mpro. Quercetin showed strong interactions with key residues in the Mpro active site in the computational analysis. In the in vitro assay, quercetin inhibited Mpro with an IC50 of 13.9 μM and exhibited low cytotoxicity (3.5% at 30 μM) in human BJ cell lines.
Bioavailability. Quercetin has low bioavailability and studies typically use advanced formulations to improve bioavailability which may be required to reach therapeutic concentrations.
59 preclinical studies support the efficacy of quercetin for COVID-19:
38 In Silico studies1-38
16 In Vitro studies8,12,14,18,35,39-49
5 In Vivo animal studies12,43,45,50,51
In Silico studies predict inhibition of SARS-CoV-2, or minimization of side effects, with quercetin or metabolites via binding to the spikeA,2,3,15,17,18,23,31,32,34,35,52,53, MproB,2,4,6,8,10,11,13,16,17,23,27,29-31,35,36,38,53,54, RNA-dependent RNA polymeraseC,2,25, PLproD,30,38, ACE2E,15,16,21,30,34,53, TMPRSS2F,15, helicaseG,22,27, endoribonucleaseH,32, cathepsin LI,19, Wnt-3J,15, FZDK,15, LRP6L,15, ezrinM,33, ADRPN,31, NRP1O,34, EP300P,9, PTGS2Q,16, HSP90AA1R,9,16, matrix metalloproteinase 9S,24, IL-6T,14,28, IL-10U,14, VEGFAV,28, and RELAW,28 proteins. In Vitro studies demonstrate efficacy in Calu-3X,41, A549Y,14, HEK293-ACE2+Z,48, Huh-7AA,18, Caco-2AB,40, Vero E6AC,12,35,40, mTECAD,43, and RAW264.7AE,43 cells. Animal studies demonstrate efficacy in K18-hACE2 miceAF,45, db/db miceAG,43,51, BALB/c miceAH,50, and rats55. Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice50.
Important missing comments or errors? Let us know.
Waqas et al., 5 Apr 2024, peer-reviewed, 10 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperQuercetinAll
Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics
Muhammad Waqas, Saeed Ullah, Sobia Ahsan Halim, Inam Ullah, Najeeb Ur Rehman, Afnan Jan, Asaad Khalid, Amjad Ali, Ajmal Khan, Ahmed Al-Harrasi
Current Medicinal Chemistry, doi:10.2174/0109298673292839240329081008
Background/Aim: The global pandemic caused by the novel SARS-CoV-2 virus underscores the urgent need for therapeutic interventions. Targeting the virus's main protease (Mpro), crucial for viral replication, is a promising strategy. Objective: The current study aims to discover novel inhibitors of Mpro. Methods: The current study identified five natural compounds (myrrhanol B (C1), myrrhanone B (C2), catechin (C3), quercetin (C4), and feralolide (C5) with strong inhibitory potential against Mpro through virtual screening and computational methods, predicting their binding efficiencies and validated it using the in-vitro inhibition activity. The selected compound's toxicity was examined using the MTT assay on a human BJ cell line. Results: Compound C1 exhibited the highest binding affinity, with a docking score of -9.82 kcal/mol and strong hydrogen bond interactions within Mpro's active site. A microscale molecular dynamics simulation confirmed the stability and tight fit of the compounds in the protein's active pocket, showing superior binding interactions. in vitro assays validated their inhibitory effects, with C1 having the most significant potency (IC50 = 2.85 µM). The non-toxic nature of these compounds in human BJ cell lines was also confirmed, advocating their safety profile. Conclusion: These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.
CONFLICT OF INTEREST The authors declare no conflict of interest, financial or otherwise.
References
Bas, Green, Al-Harrasi, Bioactive chemical constituents from the resin of Aloe vera, Z. Naturforsch. B. J. Chem. Sci, doi:10.1515/znb-2017-0117
Bhatt, Should COVID-19 mother breastfeed her new
Chang, The architecture of SARS-CoV-2 transcriptome, Cell, doi:10.1016/j.cell.2020.04.011
Dai, Zhang, Jiang, Su, Li et al., None
De Barros, Nunes, Souza, None
Dos Santos Nascimento, Da Silva-Júnior, De Aqui, None
Dos Santos Nascimento, De Moura, Would the de-[23] velopment of a multitarget inhibitor of 3CL pro and TM-PRSS2 be promising in the fight against SARS-CoV-2?, Med. Chem, doi:10.2174/1573406418666221011093439
Fanelli, Piazza, Analysis and forecast of COVID-19
Figueiredo, De Aquino, Vieira, Farias, Santos et al., The new psychoactive substances 25H-NBOMe and 25H-NBOH induce abnormal development in the zebrafish embryo and interact in the DNA major groove, Current Research in Toxicology, doi:10.1016/j.crtox.2021.11.002
Francis, None
Gao, Wang, Chen, Tepe, Huang et al., None
Genheden, Ryde, The, PBSA and MM/GBSA
Gerber, Muller, Mab, a generally applicable [] molecular force field for structure modelling in medicinal chemistry, J Comput Aided Mol Des, doi:10.1007/BF00124456
Gilbert, Commentary: SARS, MERS and COVID-19-[new threats; Old lessons, Int. J. Epidemiol, doi:10.1093/ije/dyaa061
Green, Al-Harrasi, A norterpenoid and tripenoids from Commiphora mukul : Isolation and biological activity, Z. Naturforsch. B. J. Chem. Sci, doi:10.1515/znb-2016-0062
Halim, Ahmed, Al-Harrasi, Myrrhanone B and Myrrhanol B from resin of Commipohora mukul exhibit hepatoprotective effects in-vivo, Biomed. Pharmacother, doi:10.1016/j.biopha.2021.112131
Halim, Ye, Feng, Yu, Wang et al., In silico prediction of novel inhibitors of sars--[27] cov-2 main protease through structure-based virtual screening and molecular dynamic simulation, Pharmaceuticals, doi:10.3390/ph14090896
Han, Lindsey, Rico, Romigh, Goins, SARS-CoV-2 3CL-protease inhibitors derived from ML300: Investigation of P1 and replacements of the 1,2,3-benzotriazole, Res Sq, doi:10.21203/rs.3.rs-2880312/v1
He, Deng, Li, Coronavirus disease, What
Hemaiswarya, Kruthiventi, Doble, Synergism [25] between natural products and antibiotics against infectious diseases, Phytomedicine, doi:10.1016/j.phymed.2008.06.008
Hooper, Macdonald, Reilly, Maw, Wirrick, None
Huang, Migues, Bickel, Wang, Pincay et al., ff19SB: Amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution, J. Chem. Theory Comput, doi:10.1021/acs.jctc.9b00591
Jackson, Farzan, Chen, Choe, Mech-[14] anisms of SARS-CoV-2 entry into cells, Nat. Rev. Mol. Cell Biol, doi:10.1038/s41580-021-00418-x
Jakalian, Bush, Jack, Bayly, Wang et al., Fast, effi-[cient generation of high-quality atomic charges. AM1-BCC model: I, Method. J. Comput. Chem, doi:10.1002/(SICI)1096-987X(20000130)21:2<132::AID-JCC5>3.0.CO;2-P
Jan, Muhsinah, Khan, Al-Harrasi, Targeting papain-like protease by natural products as novel therapeutic potential SARS-CoV-2, Int. J. Biol. Macromol, doi:10.1016/j.ijbiomac.2023.128812
Jo, Kim, Kim, Kim, Shin, Flavonoids with inhibitory activity against SARS-CoV-2 3CLpro, J. Enzyme Inhib. Med. Chem, doi:10.1080/14756366.2020.1801672
Khamto, Utama, Tateing, Sangthong, None
Khan, Gul, Rehman, Khan, Karim, None
Khan, Khan, Abbas, Rafiq, Al-Harrasi, Antiproliferative and carbonic anhydrase II inhibitory potential of chemical constituents from Lycium shawii and aloe vera: Evidence from in silico target fishing and in vitro testing, Pharmaceuticals, doi:10.3390/ph13050094
Kim, Lee, Yang, Kim, Kim, None
Kim, Marks, Clemens, Looking beyond [12] COVID-19 vaccine phase 3 trials, Nat. Med, doi:10.1038/s41591-021-01230-y
Kräutler, Van Gunsteren, Hünenberger, ; V Roe, Cheatham, fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations, J. Chem. Theory Comput, doi:10.1021/ct400341p
Li, Bai, Hashikawa, The neuroinvasive po-[4] tential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients, J. Med. Virol, doi:10.1002/jmv.25728
Mahdi, Mótyán, Szojka, Golda, Miczi, None
Mengist, Dilnessa, Jin, Structural basis of po-[15] tential inhibitors targeting SARS-CoV-2 main protease, Front Chem, doi:10.3389/fchem.2021.622898
Mohammed, Zhao, Yang, Xie, Ding et al., Biochemical characterization of SARS-CoV-2 nucleocapsid protein, Biochem. Biophys. Res. Commun, doi:10.1016/j.bbrc.2020.04.136
Ndwandwe, Wiysonge, COVID-19 vaccines, Curr. Opin. Immunol, doi:10.1016/j.coi.2021.07.003
Onufriev, Bashford, Case, Exploring protein [46] native states and large-scale conformational changes with a modified generalized born model, Proteins, doi:10.1002/prot.20033
Raymenants, André, Leyssen, Neyts, Jochmans et al., molnupiravir and nirmatrelvir remain active against SARS-CoV-2 omicron and other variants of concern, Antiviral Res, doi:10.1016/j.antiviral.2022.105252
Rehman, Hussain, Ali, Khan, Mabood, None
Rehman, Hussain, Khan, Csuk, Abbas, None
Rehman, Hussain, Khiat, Khan, Ab, None
Rithchumpon, Cheechana, Saiai, Semakul, Punyodom et al., Discovery of natural bisbenzylisoquinoline analogs from the library of thai traditional plants as SARS-CoV-2 3CL pro inhibitors: In silico molecular docking, molecular dynamics, and in vitro enzymatic activity, J. Chem. Inf. Model, doi:10.1021/acs.jcim.2c01309
Rohaim, El Naggar, Clayton, Munir, Structural and functional insights into non-structural proteins of coronaviruses, Microb. Pathog, doi:10.1016/j.micpath.2020.104641
Salomon-Ferrer, Götz, Poole, Le Grand, None
Shahrajabian, Sun, Shen, Cheng, Chinese, None
Shinwari, Hussain, Al-Harrasi, Chemical constituents of acridocarpus orientalis and their chemotaxonomic significance, Chem. Nat. Compd, doi:10.1007/s10600-019-02752-1
Sindhikara, Kim, Voter, Roitberg, Bad [seeds sprout perilous dynamics: Stochastic thermostat induced trajectory synchronization in biomolecules, J. Chem. Theory Comput, doi:10.1021/ct800573m
Sinha, Gadhwal, Joshi, Srivastava, Govil, None
Speranza, Manitto, Cassara, Monti, Fer-, alolide, a dihydroisocoumarin from cape aloe, Phytochemistry, doi:10.1016/0031-9422(93)85417-P
Swift, GraphPad prism, data analysis, and scientific
Tadesse, Muluye, The impact of COVID-19 pan-[demic on education system in developing countries: A review, Open Journal of Social Sciences, doi:10.4236/jss.2020.810011
Tian, Kasavajhala, Belfon, Raguette, None
Tőzsér, Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2′s main protease, Virol. J, doi:10.1186/s12985-020-01457-0
Ur Rehman, Halim, Khan, Hussain, Yar, None
Vangeel, Chiu, De Jonghe, Maes, Slechten, None
Vassetti, Pagliai, Procacci, Assessment of GAF-[F2 and OPLS-AA general force fields in combination with the water models TIP3P, SPCE, and OPC3 for the solvation free energy of druglike organic molecules, J. Chem. Theory Comput, doi:10.1021/acs.jctc.8b01039
Walker, Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle mesh ewald, J. Chem. Theory Comput, doi:10.1021/ct400314y
Waqas, Ullah, Halim, Rehman, Ali, None
Weiser, Shenkin, Still, Aquino, Silva-Júnior, Approximate atomic [surfaces from linear combinations of pairwise overlaps (L-CPO), J. Comput. Chem, doi:10.1002/(SICI)1096-987X(19990130)20:2<217::AID-JCC4>3.0.CO;2-A
Wen, Scoles, Facelli, Molecular dynamics [44] analysis of the aggregation propensity of polyglutamine segments, PLoS One, doi:10.1371/journal.pone.0178333
Xie, Jin, Peng, Liu, Structure-based design, synthesis and biological evaluation of peptidomimetic aldehydes as a novel series of antiviral drug candidates targeting the SARS-CoV-2 main protease, BioRxiv
Zeng, Liu, Ma, Zhao, Yang et al., None
Zhao, Sun, Huang, Niu, Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease, Nat. Commun, doi:10.1038/s41467-020-18233-x
Ziegel, Numerical recipes: The art of scientific com
Zor, Aydin, Güner, Başaran, Başaran, None
Şiṁşek Yavuz, Komşuoğlu Çelikyurt, An update of
{ 'indexed': {'date-parts': [[2024, 4, 10]], 'date-time': '2024-04-10T00:46:20Z', 'timestamp': 1712709980570}, 'reference-count': 0, 'publisher': 'Bentham Science Publishers Ltd.', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2024, 4, 5]]}, 'abstract': '<jats:sec>\n' '<jats:title>Background/Aim:</jats:title>\n' '<jats:p>The global pandemic caused by the novel SARS-CoV-2\n' "virus underscores the urgent need for therapeutic interventions. Targeting the virus's\n" 'main protease (Mpro), crucial for viral replication, is a promising strategy.</jats:p>\n' '</jats:sec>\n' '<jats:sec>\n' '<jats:title>Objective:</jats:title>\n' '<jats:p>The current study aims to discover novel inhibitors of Mpro.</jats:p>\n' '</jats:sec>\n' '<jats:sec>\n' '<jats:title>Methods:</jats:title>\n' '<jats:p>The current study identified five natural compounds (myrrhanol B (C1), myrrhanone\n' 'B (C2), catechin (C3), quercetin (C4), and feralolide (C5) with strong inhibitory\n' 'potential against Mpro through virtual screening and computational methods, predicting\n' 'their binding efficiencies and validated it using the in-vitro inhibition activity. The\n' "selected compound's toxicity was examined using the MTT assay on a human BJ cell\n" 'line.</jats:p>\n' '</jats:sec>\n' '<jats:sec>\n' '<jats:title>Results:</jats:title>\n' '<jats:p>Compound C1 exhibited the highest binding affinity, with a docking score of\n' "-9.82 kcal/mol and strong hydrogen bond interactions within Mpro's active site. A microscale\n" 'molecular dynamics simulation confirmed the stability and tight fit of the compounds\n' "in the protein's active pocket, showing superior binding interactions. in vitro assays\n" 'validated their inhibitory effects, with C1 having the most significant potency\n' '(IC50 = 2.85 μM). The non-toxic nature of these compounds in human BJ cell lines was\n' 'also confirmed, advocating their safety profile.</jats:p>\n' '</jats:sec>\n' '<jats:sec>\n' '<jats:title>Conclusion:</jats:title>\n' '<jats:p>These findings highlight the effectiveness of combining computational and\n' 'experimental approaches to identify potential lead compounds for SARS-CoV-2, with\n' 'C1-C5 emerging as promising candidates for further drug development against this\n' 'virus.</jats:p>\n' '</jats:sec>\n' '<jats:sec>\n' '<jats:title>conclusion:</jats:title>\n' '<jats:p>These findings highlight the effectiveness of combining computational and ' 'experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 ' 'emerging as promising candidates for further drug development against this virus.</jats:p>\n' '</jats:sec>', 'DOI': '10.2174/0109298673292839240329081008', 'type': 'journal-article', 'created': {'date-parts': [[2024, 4, 9]], 'date-time': '2024-04-09T08:47:12Z', 'timestamp': 1712652432000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to ' 'Antiviral Therapeutics', 'prefix': '10.2174', 'volume': '31', 'author': [ { 'given': 'Muhammad', 'family': 'Waqas', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Biotechnology and Genetic Engineering, Hazara ' 'University Mansehra, Mansehra 2100, Pakistan'}]}, { 'given': 'Saeed', 'family': 'Ullah', 'sequence': 'additional', 'affiliation': [ { 'name': 'Natural and Medical Sciences Research Center, University of ' 'Nizwa, Nizwa 616, Sultanate of Oman'}]}, { 'given': 'Sobia', 'family': 'Ahsan Halim', 'sequence': 'additional', 'affiliation': [ { 'name': 'Natural and Medical Sciences Research Center, University of ' 'Nizwa, Nizwa 616, Sultanate of Oman'}]}, { 'given': 'Inam', 'family': 'Ullah', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Biotechnology and Genetic Engineering, Hazara ' 'University Mansehra, Mansehra 2100, Pakistan'}]}, { 'family': 'Najeeb Ur Rehman', 'sequence': 'additional', 'affiliation': [ { 'name': 'Natural and Medical Sciences Research Center, University of ' 'Nizwa, Nizwa 616, Sultanate of Oman'}]}, { 'given': 'Afnan', 'family': 'Jan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Umm Al-Qura University, Faculty of Medicine, Department of ' 'Biochemistry, Makkah, Kingdom of Saudi Arabia'}]}, { 'given': 'Asaad', 'family': 'Khalid', 'sequence': 'additional', 'affiliation': [ { 'name': 'Substance Abuse and Toxicology Research Center, Jazan ' 'University, P.O. Box: 114, Jazan 45142, Saudi Arabia'}]}, { 'given': 'Amjad', 'family': 'Ali', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Biotechnology and Genetic Engineering, Hazara ' 'University Mansehra, Mansehra 2100,\n' 'Pakistan'}]}, { 'given': 'Ajmal', 'family': 'Khan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Natural and Medical Sciences Research Center, University of ' 'Nizwa, Nizwa 616, Sultanate of Oman'}]}, { 'given': 'Ahmed', 'family': 'Al-Harrasi', 'sequence': 'additional', 'affiliation': [ { 'name': 'Natural and Medical Sciences Research Center, University of ' 'Nizwa, Nizwa 616, Sultanate of Oman'}]}], 'member': '965', 'container-title': 'Current Medicinal Chemistry', 'original-title': [], 'language': 'en', 'deposited': { 'date-parts': [[2024, 4, 9]], 'date-time': '2024-04-09T08:47:21Z', 'timestamp': 1712652441000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.eurekaselect.com/228703/article'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 4, 5]]}, 'references-count': 0, 'alternative-id': ['LiveAll1'], 'URL': 'http://dx.doi.org/10.2174/0109298673292839240329081008', 'relation': {}, 'ISSN': ['0929-8673'], 'subject': ['Pharmacology', 'Molecular Medicine', 'Drug Discovery', 'Biochemistry', 'Organic Chemistry'], 'container-title-short': 'CMC', 'published': {'date-parts': [[2024, 4, 5]]}}
Loading..
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment 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   
Submit    
Post
Share
@CovidAnalysis
FAQ
Public domain CC0 1.0