Conv. Plasma
Nigella Sativa

All quercetin studies
Meta analysis
study COVID-19 treatment researchQuercetinQuercetin (more..)
Melatonin Meta
Azvudine Meta Metformin Meta
Bromhexine Meta
Budesonide Meta Molnupiravir Meta
Colchicine Meta
Conv. Plasma Meta
Curcumin Meta Nigella Sativa Meta
Famotidine Meta Nitazoxanide Meta
Favipiravir Meta Paxlovid Meta
Fluvoxamine Meta Quercetin Meta
Hydroxychlor.. Meta Remdesivir Meta
Ivermectin Meta
Lactoferrin Meta

All Studies   Meta Analysis   Recent:  

Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein

Moschovou et al., International Journal of Molecular Sciences, doi:10.3390/ijms242115894
Nov 2023  
  Source   PDF   All Studies   Meta AnalysisMeta
In Silico molecular docking and molecular dynamics analysis identifying curcumin, quercetin, rosmarinic acid, and salvianolic acid B as having favorable binding to Mpro and three distinct sites on the S protein. Molecular dynamics simulations confirmed rosmarinic acid and quercetin's stable binding to Mpro. At the S protein sites, salvianolic acid B and rosmarinic acid formed robust complexes. A similarity search yielded compounds structurally related to the top binders, with two analogs of salvianolic acid emerging as promising multi-target inhibitors against both Mpro and S proteins.
This study includes quercetin and curcumin.
Moschovou et al., 2 Nov 2023, peer-reviewed, 7 authors.
In Silico 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 PaperQuercetinAll
Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein
Kalliopi Moschovou, Maria Antoniou, Eleni Chontzopoulou, Konstantinos D Papavasileiou, Georgia Melagraki, Antreas Afantitis, Thomas Mavromoustakos
International Journal of Molecular Sciences, doi:10.3390/ijms242115894
In this in silico study, we conducted an in-depth exploration of the potential of natural products and antihypertensive molecules that could serve as inhibitors targeting the key proteins of the SARS-CoV-2 virus: the main protease (Mpro) and the spike (S) protein. By utilizing Induced Fit Docking (IFD), we assessed the binding affinities of the molecules under study to these crucial viral components. To further comprehend the stability and molecular interactions of the "proteinligand" complexes that derived from docking studies, we performed molecular dynamics (MD) simulations, shedding light on the molecular basis of potential drug candidates for COVID-19 treatment. Moreover, we employed Molecular Mechanics Generalized Born Surface Area (MM-GBSA) calculations on all "protein-ligand" complexes, underscoring the robust binding capabilities of rosmarinic acid, curcumin, and quercetin against Mpro, and salvianolic acid b, rosmarinic acid, and quercetin toward the S protein. Furthermore, in order to expand our search for potent inhibitors, we conducted a structure similarity analysis, using the Enalos Suite, based on the molecules that indicated the most favored results in the in silico studies. The Enalos Suite generated 115 structurally similar compounds to salvianolic acid, rosmarinic acid, and quercetin. These compounds underwent IFD calculations, leading to the identification of two salvianolic acid analogues that exhibited strong binding to all the examined binding sites in both proteins, showcasing their potential as multi-target inhibitors. These findings introduce exciting possibilities for the development of novel therapeutic agents aiming to effectively disrupt the SARS-CoV-2 virus lifecycle.
Adem, Eyupoglu, Sarfraz, Rasul, Ali, Identification of Potent COVID-19 Main Protease (Mpro) Inhibitors from Natural Polyphenols: An in Silico Strategy Unveils a Hope against CORONA, doi:10.20944/preprints202003.0333.v1
Adem, Eyupoglu, Sarfraz, Rasul, Zahoor et al., Caffeic acid derivatives (CAFDs) as inhibitors of SARS-CoV-2: CAFDs-based functional foods as a potential alternative approach to combat COVID-19, Phytomedicine, doi:10.1016/j.phymed.2020.153310
Afantitis, Tsoumanis, Melagraki, Enalos suite of tools: Enhance cheminformatics and nanoinformat-ics through knime, Curr. Med. Chem, doi:10.2174/0929867327666200727114410
Ali, Vijayan, Dynamics of the ACE2-SARS-CoV-2/SARS-CoV spike protein interface reveal unique mechanisms, Sci. Rep, doi:10.1038/s41598-020-71188-3
Alzaabi, Hamdy, Ashmawy, Hamoda, Alkhayat et al., Flavonoids are promising safe therapy against COVID-19, Phytochem. Rev, doi:10.1007/s11101-021-09759-z
Amin, Tabari, Iranpanah, Bahramsoltani, Rahimi, Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review, Molecules, doi:10.3390/molecules26133900
Armstrong, Soltoff, Rieu-Werden, Metlay, Haas, Use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers associated with lower risk of COVID-19 in household contacts, PLoS ONE, doi:10.1371/journal.pone.0247548
Bahun, Jukić, Oblak, Kranjc, Bajc et al., Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols, Food Chemistry, doi:10.1016/j.foodchem.2021.131594
Behloul, Baha, Guo, Yang, Shi et al., In silico identification of strong binders of the SARS-CoV-2 receptorbinding domain, Eur. J. Pharmacol, doi:10.1016/j.ejphar.2020.173701
Bhati, Kaushik, Singh, Rational design of flavonoid based potential inhibitors targeting SARS-CoV 3CL protease for the treatment of COVID-19, J. Mol. Struct, doi:10.1016/j.molstruc.2021.130380
Bojadzic, Alcazar, Chen, Chuang, Condor Capcha et al., Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2, ACS Infect. Dis, doi:10.1021/acsinfecdis.1c00070
Chakravarti, Singh, Ghosh, Dey, Sharma et al., A review on potential of natural products in the management of COVID-19, RSC Adv, doi:10.1039/D1RA00644D
Cherrak, Merzouk, Mokhtari-Soulimane, Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies, PLoS ONE, doi:10.1371/journal.pone.0240653
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
Dhar, Prasad, Tiwari, Pankaj, Bano et al., An In-Silico Study to Identify Hidden Features of Spike Protein and Main Protease of SARS-CoV-2, Preprints
Duarte, Pelorosso, Nicolosi, Victoria Salgado, Vetulli et al., Telmisartan for treatment of COVID-19 patients: An open multicenter randomized clinical trial, EClinicalMedicine, doi:10.1016/j.eclinm.2021.100962
Durdagi, Avsar, Orhan, Serhatli, Balcioglu et al., The neutralization effect of montelukaston SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies, Mol. Ther, doi:10.1016/j.ymthe.2021.10.014
Elebeedy, Elkhatib, Kandeil, Ghanem, Kutkat et al., Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational andin vitroinsights, RSC Adv, doi:10.1039/D1RA05268C
Forrester, Booz, Sigmund, Coffman, Kawai et al., Angiotensin II signal transduction: An update on mechanisms of physiology and pathophysiology, Physiol. Rev, doi:10.1152/physrev.00038.2017
Han, Král, Computational Design of ACE2-Based Peptide Inhibitors of SARS-CoV-2, ACS Nano, doi:10.1021/acsnano.0c02857
Hoffmann, Kleine-Weber, Schroeder, Krüger, 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
Hu, Wang, Zhang, Bai, Wang et al., Three salvianolic acids inhibit 2019-nCoV spike pseudovirus viropexis by binding to both its RBD and receptor ACE2, J. Med. Virol, doi:10.1002/jmv.26874
Huang, Yang, Xu, Xu, Liu, Structural and functional properties of SARS-CoV-2 spike protein: Potential antivirus drug development for COVID-19, Acta Pharmacol. Sin, doi:10.1038/s41401-020-0485-4
Jain, Mujwar, Repurposing metocurine as main protease inhibitor to develop novel antiviral therapy for COVID-19, Struct. Chem, doi:10.1007/s11224-020-01605-w
Jeon, Ko, Lee, Choi, Byun et al., Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs, Antimicrob. Agents Chemother, doi:10.1128/AAC.00819-20
Jin, Du, Xu, Deng, Liu et al., Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors, Nature, doi:10.1038/s41586-020-2223-y
Jorgensen, Chandrasekhar, Madura, Impey, Klein, Comparison of simple potential functions for simulating liquid water, J. Chem. Phys, doi:10.1063/1.445869
Jorgensen, Maxwell, Tirado-Rives, Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids, J. Am. Chem. Soc, doi:10.1021/ja9621760
Kaminski, Friesner, Tirado-Rives, Jorgensen, Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides, J. Phys. Chem, doi:10.1021/jp003919d
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), Phyther. Res, doi:10.1002/ptr.6998
Lan, Ge, Yu, Shan, Zhou et al., Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor, Nature, doi:10.1038/s41586-020-2180-5
Li, Abel, Zhu, Cao, Zhao et al., The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling, Proteins Struct. Funct. Bioinform, doi:10.1002/prot.23106
Li, Zhou, Guo, Xie, He et al., Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2, J. Transl. Med, doi:10.1186/s12967-022-03501-9
Lu, Stratton, Tang, Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle, J. Med. Virol, doi:10.1002/jmv.25678
Lyne, Lamb, Saeh, Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring, J. Med. Chem, doi:10.1021/jm060522a
Mavromoustakos, Agelis, Durdagi, AT1 antagonists: A patent review (2008-2012, Expert Opin. Ther. Pat, doi:10.1517/13543776.2013.830104
Merarchi, Dudha, Das, Garg, Natural products and phytochemicals as potential anti-SARS-CoV-2 drugs, Phytother. Res, doi:10.1002/ptr.7151
Onweni, Zhang, Caulfield, Hopkins, Fairweather et al., ACEI/ARB therapy in COVID-19: The double-edged sword of ACE2 and SARS-CoV-2 viral docking, Crit. Care, doi:10.1186/s13054-020-03195-9
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
Qian, Ou, Góes, Osborne, Castano et al., Identification of the Receptor-Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1, J. Virol, doi:10.1128/JVI.03737-14
Qiu, Shenkin, Hollinger, Still, The GB/SA continuum model for solvation. A fast analytical method for the calculation of approximate Born radii, J. Phys. Chem. A, doi:10.1021/jp961992r
Rashid, Xie, Suleman, Shah, Khan et al., Roles and functions of SARS-CoV-2 proteins in host immune evasion, Front. Immunol, doi:10.3389/fimmu.2022.940756
Roy, Sk, Tanwar, Kar, Computational studies indicated the effectiveness of human metabolites against SARS-CoV-2 main protease, Mol. Divers, doi:10.1007/s11030-022-10513-6
Rungruangmaitree, Phoochaijaroen, Chimprasit, Saparpakorn, Pootanakit et al., Structural analysis of the coronavirus main protease for the design of pan-variant inhibitors, Sci. Rep, doi:10.1038/s41598-023-34305-6
Russo, Tedesco, Spagnuolo, Russo, Antioxidant polyphenols in cancer treatment: Friend, foe or foil? Semin, Cancer Biol, doi:10.1016/j.semcancer.2017.05.005
Samy, Karunanithi, Sheshadhri, Rengarajan, Srinivasan et al., R)-(+)-Rosmarinic Acid as an Inhibitor of Herpes and Dengue Virus Replication: An In Silico Assessment, Rev. Bras. Farmacogn, doi:10.1007/s43450-023-00381-y
Schwantes, Pande, Bowers, Chow, Xu et al., Will Cannabis or Cannabinoids Protect You from SARS-CoV-2 Infection or Treat COVID-19?, J. Chem. Theory Comput, doi:10.1159/000522472
Shahhamzehei, Abdelfatah, Efferth, In Silico and In Vitro Identification of Pan-Coronaviral Main Protease Inhibitors from a Large Natural Product Library, Pharmaceuticals, doi:10.3390/ph15030308
Shinoda, Mikami, Rigid-body dynamics in the isothermal-isobaric ensemble: A test on the accuracy and computational efficiency, J. Comput. Chem, doi:10.1002/jcc.10249
Spagnuolo, Moccia, Russo, Anti-inflammatory effects of flavonoids in neurodegenerative disorders, Eur. J. Med. Chem, doi:10.1016/j.ejmech.2017.09.001
Sriram, Insel, A hypothesis for pathobiology and treatment of COVID-19: The centrality of ACE1/ACE2 imbalance, Br. J. Pharmacol, doi:10.1111/bph.15082
Still, Tempczyk, Hawley, Hendrickson, Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics, J. Am. Chem. Soc, doi:10.1021/ja00172a038
Suite, Protein Preparation Wizard; Epik Version 2.3
Van Breemen, Muchiri, Bates, Weinstein, Leier et al., Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants, J. Nat. Prod, doi:10.1021/acs.jnatprod.1c00946
Varsou, Nikolakopoulos, Tsoumanis, Melagraki, Afantitis et al., Suite: New Cheminformatics Platform for Drug Discovery and Computational Toxicology
Xu, Gao, Liang, Chen, In silico screening of potential anti-COVID-19 bioactive natural constituents from food sources by molecular docking, Nutrition, doi:10.1016/j.nut.2020.111049
Yang, Pan, Xu, Cheng, Huang et al., Salvianolic acid C potently inhibits SARS-CoV-2 infection by blocking the formation of six-helix bundle core of spike protein, Signal Transduct. Target. Ther, doi:10.1038/s41392-020-00325-1
Zhang, Lin, Sun, Curth, Drosten et al., Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors, Science, doi:10.1126/science.abb3405
Zhu, Zhang, Wang, Li, Yang et al., A Novel Coronavirus from Patients with Pneumonia in China, N. Engl. J. Med, doi:10.1056/NEJMoa2001017
Please send us corrections, updates, or comments. c19early involves the extraction of over 100,000 datapoints from thousands of papers. Community updates help ensure high accuracy. 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