12 results on '"Ceballos-Laita, Laura"'
Search Results
2. Effects of Fe and Mn Deficiencies on the Root Protein Profiles of Tomato (Solanum lycopersicum) Using Two-Dimensional Electrophoresis and Label-Free Shotgun Analyses
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Ceballos-Laita, Laura, primary, Takahashi, Daisuke, additional, Uemura, Matsuo, additional, Abadía, Javier, additional, López-Millán, Ana Flor, additional, and Rodríguez-Celma, Jorge, additional
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- 2022
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3. l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells
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Sancineto, Luca, primary, Ostacolo, Carmine, additional, Ortega-Alarcon, David, additional, Jimenez-Alesanco, Ana, additional, Ceballos-Laita, Laura, additional, Vega, Sonia, additional, Abian, Olga, additional, Velazquez-Campoy, Adrian, additional, Moretti, Silvia, additional, Dabrowska, Agnieszka, additional, Botwina, Pawel, additional, Synowiec, Aleksandra, additional, Kula-Pacurar, Anna, additional, Pyrc, Krzysztof, additional, Iraci, Nunzio, additional, and Santi, Claudio, additional
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- 2021
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4. Sub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural Compounds
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Rizzuti, Bruno, primary, Ceballos-Laita, Laura, additional, Ortega-Alarcon, David, additional, Jimenez-Alesanco, Ana, additional, Vega, Sonia, additional, Grande, Fedora, additional, Conforti, Filomena, additional, Abian, Olga, additional, and Velazquez-Campoy, Adrian, additional
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- 2021
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5. Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of Mpro and Its Antiviral Activity in Cells against SARS-CoV-2
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Mangiavacchi, Francesca, primary, Botwina, Pawel, additional, Menichetti, Elena, additional, Bagnoli, Luana, additional, Rosati, Ornelio, additional, Marini, Francesca, additional, Fonseca, Sérgio F., additional, Abenante, Laura, additional, Alves, Diego, additional, Dabrowska, Agnieszka, additional, Kula-Pacurar, Anna, additional, Ortega-Alarcon, David, additional, Jimenez-Alesanco, Ana, additional, Ceballos-Laita, Laura, additional, Vega, Sonia, additional, Rizzuti, Bruno, additional, Abian, Olga, additional, Lenardão, Eder J., additional, Velazquez-Campoy, Adrian, additional, Pyrc, Krzysztof, additional, Sancineto, Luca, additional, and Santi, Claudio, additional
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- 2021
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6. Rutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs
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Rizzuti, Bruno, primary, Grande, Fedora, additional, Conforti, Filomena, additional, Jimenez-Alesanco, Ana, additional, Ceballos-Laita, Laura, additional, Ortega-Alarcon, David, additional, Vega, Sonia, additional, Reyburn, Hugh T., additional, Abian, Olga, additional, and Velazquez-Campoy, Adrian, additional
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- 2021
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7. Thermal Liquid Biopsy (TLB) Focused on Benign and Premalignant Pancreatic Cyst Diagnosis
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Hermoso-Durán, Sonia, primary, García-Rayado, Guillermo, additional, Ceballos-Laita, Laura, additional, Sostres, Carlos, additional, Vega, Sonia, additional, Millastre, Judith, additional, Sánchez-Gracia, Oscar, additional, Ojeda, Jorge L., additional, Lanas, Ángel, additional, Velázquez-Campoy, Adrián, additional, and Abian, Olga, additional
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- 2020
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8. Effects of Excess Manganese on the Xylem Sap Protein Profile of Tomato (Solanum lycopersicum) as Revealed by Shotgun Proteomic Analysis
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Ceballos-Laita, Laura, primary, Gutierrez-Carbonell, Elain, additional, Takahashi, Daisuke, additional, Lonsdale, Andrew, additional, Abadía, Anunciación, additional, Doblin, Monika S., additional, Bacic, Antony, additional, Uemura, Matsuo, additional, Abadía, Javier, additional, and López-Millán, Ana Flor, additional
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- 2020
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9. γ-Lindane Increases Microcystin Synthesis in Microcystis aeruginosa PCC7806
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Ceballos-Laita, Laura, primary, Calvo-Begueria, Laura, additional, Lahoz, Jessica, additional, Bes, María-Teresa, additional, Fillat, María, additional, and Peleato, María-Luisa, additional
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- 2015
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10. Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of Mpro and Its Antiviral Activity in Cells against SARS-CoV-2
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Diego Alves, Laura Ceballos-Laita, Bruno Rizzuti, Krzysztof Pyrc, Sonia Vega, Luana Bagnoli, Eder J. Lenardão, Ana Jiménez-Alesanco, Pawel Botwina, David Ortega-Alarcon, Ornelio Rosati, Francesca Marini, Agnieszka Dabrowska, Francesca Mangiavacchi, Olga Abian, Adrián Velázquez-Campoy, Luca Sancineto, Anna Kula-Pacurar, Laura Abenante, Claudio Santi, Elena Menichetti, Sergio F. Fonseca, Università degli Studi di Perugia, Instituto de Salud Carlos III, Fundación hna, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Diputación General de Aragón, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Financiadora de Estudos e Projetos (Brasil), Ministry of Science and Higher Education (Poland), Botwina, Pawel [0000-0001-9006-1568], Bagnoli, Luana [0000-0002-0622-4561], Marini, Francesca [0000-0003-0747-5060], Alves, Diego [0000-0002-1074-0294], Dabrowska, Agnieszka [0000-0003-1499-4950], Kula-Pacurar, Anna [0000-0001-8404-2176], Ceballos-Laita, Laura [0000-0002-7223-1719], Rizzuti, Bruno [0000-0003-1110-764X], Lenardão, Eder J. [0000-0001-7920-3289], Velázquez-Campoy, Adrián [0000-0001-5702-4538], Pyrc, Krzysztof [0000-0002-3867-7688], Sancineto, Luca [0000-0002-6199-7399], Santi, Claudio [0000-0002-7698-8970], Botwina, Pawel, Bagnoli, Luana, Marini, Francesca, Alves, Diego, Dabrowska, Agnieszka, Kula-Pacurar, Anna, Ceballos-Laita, Laura, Rizzuti, Bruno, Lenardão, Eder J., Velázquez-Campoy, Adrián, Pyrc, Krzysztof, Sancineto, Luca, and Santi, Claudio
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0301 basic medicine ,medicine.medical_treatment ,Flavonoid ,Virus Replication ,01 natural sciences ,chemistry.chemical_compound ,Catalytic Domain ,Chlorocebus aethiops ,Biology (General) ,selenium ,Spectroscopy ,chemistry.chemical_classification ,General Medicine ,Computer Science Applications ,Molecular Docking Simulation ,Chemistry ,Biochemistry ,Quercetin ,flavanols ,QH301-705.5 ,Antiviral Agents ,Catalysis ,Article ,Flavanols ,Inorganic Chemistry ,Viral Matrix Proteins ,03 medical and health sciences ,Selenium ,medicine ,Animals ,Humans ,Protease Inhibitors ,Physical and Theoretical Chemistry ,Binding site ,Molecular Biology ,IC50 ,Vero Cells ,QD1-999 ,Protease ,Binding Sites ,010405 organic chemistry ,SARS-CoV-2 ,Organic Chemistry ,COVID-19 ,Hydrogen Bonding ,In vitro ,0104 chemical sciences ,030104 developmental biology ,chemistry ,Viral replication ,Docking (molecular) ,main protease ,Main protease - Abstract
The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 μM and 8 μM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile, This work was supported by the University of Perugia “Fondo per la Ricerca di Base 2019”(C.S.); Fundación hna (to A.V.C. and O.A.); Miguel Servet Program from Instituto de Salud Carlos III (CPII13/00017 to O.A.); Fondo de Investigaciones Sanitarias from the Instituto de Salud Carlos III, and the European Union (ERDF/ESF, “Investing in your future”) (PI18/00349 to O.A. and an FIS Research Contract to L.C.L.); Spanish Ministry of Economy and Competitiveness (BFU2016-78232-P to A.V.C.); Spanish Ministry of Science, Innovation and Universities (FPI Predoctoral Research Contract BES-2017-080739 to D.O.A.); Diputación General de Aragón (Predoctoral Research Contract 2019 to A.J.A., “Protein Targets and Bioactive Compounds Group” E45_20R to A.V.C., “Digestive Pathology Group” B25_20R to O.A.); and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. FAPERGS, CNPq, and FINEP are acknowledged for financial support. CNPq is also acknowledged for fellowships to E.J.L. and D.A. This work was supported by the subsidy from the Polish Ministry of Science and Higher Education for research on the
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- 2021
11. Rutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs
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Fedora Grande, Olga Abian, David Ortega-Alarcon, Adrián Velázquez-Campoy, Bruno Rizzuti, Filomena Conforti, Ana Jiménez-Alesanco, Laura Ceballos-Laita, Hugh T. Reyburn, Sonia Vega, Fundación hna, Instituto de Salud Carlos III, European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Diputación General de Aragón, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Rizzuti, Bruno [0000-0003-1110-764X], Grande, Fedora [0000-0002-6154-4330], Conforti, Filomena [0000-0001-6699-005X], Ceballos-Laita, Laura [0000-0002-7223-1719], Abian, Olga [0000-0001-5664-1729], Velázquez-Campoy, Adrián [0000-0001-5702-4538], Rizzuti, Bruno, Grande, Fedora, Conforti, Filomena, Ceballos-Laita, Laura, Abian, Olga, and Velázquez-Campoy, Adrián
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0301 basic medicine ,spectroscopy ,Molecular model ,Chemical structure ,medicine.medical_treatment ,Rutin ,enzyme inhibitors ,Flavonoid ,Medicine (miscellaneous) ,Molecular modeling ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Article ,quercetin ,03 medical and health sciences ,chemistry.chemical_compound ,antivirals ,In vivo ,medicine ,Drug selection ,lcsh:QH301-705.5 ,Spectroscopy ,chemistry.chemical_classification ,Protease ,010405 organic chemistry ,Chemistry ,molecular modeling ,SARS-CoV-2 ,rutin ,Enzyme inhibitors ,Antivirals ,0104 chemical sciences ,030104 developmental biology ,Biochemistry ,lcsh:Biology (General) ,Docking (molecular) ,Quercetin ,drug selection - Abstract
The pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has stimulated the search for antivirals to tackle COVID-19 infection. Molecules with known pharmacokinetics and already approved for human use have been demonstrated or predicted to be suitable to be used either directly or as a base for a scaffold-based drug design. Among these substances, quercetin is known to be a potent in vitro inhibitor of 3CLpro, the SARS-CoV-2 main protease. However, its low in vivo bioavailability calls for modifications to its molecular structure. In this work, this issue is addressed by using rutin, a natural flavonoid that is the most common glycosylated conjugate of quercetin, as a model. Combining experimental (spectroscopy and calorimetry) and simulation techniques (docking and molecular dynamics simulations), we demonstrate that the sugar adduct does not hamper rutin binding to 3CLpro, and the conjugated compound preserves a high potency (inhibition constant in the low micromolar range, Ki = 11 μM). Although showing a disruption of the pseudo-symmetry in the chemical structure, a larger steric volume and molecular weight, and a higher solubility compared to quercetin, rutin is able to associate in the active site of 3CLpro, interacting with the catalytic dyad (His41/Cys145). The overall results have implications in the drug-design of quercetin analogs, and possibly other antivirals, to target the catalytic site of the SARS-CoV-2 3CLpro, This work was supported by Fundación hna (to A.V.C. and O.A.); Miguel Servet Program from Instituto de Salud Carlos III (CPII13/00017 to O.A.); Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III, and European Union (ERDF/ESF, ‘Investing in your future’) (PI18/00349 to O.A. and a FIS Research Contract to L.C.-L.); Spanish Ministry of Economy and Competitiveness (BFU2016-78232-P to A.V.-C. and SAF2017-83265-R to H.T.R.); Spanish Ministry of Science, Innovation and Universities (FPI Predoctoral Research Contract BES-2017-080739 to D.O.-A.); the Spanish National Research Council (CSIC, project 202020E079); Diputación General de Aragón (Predoctoral Research Contract 2019 to A.J.-A., ‘Protein Targets and Bioactive Compounds Group’ E45_20R to A.V.-C., ‘Digestive Pathology Group’ B25_20R to O.A.); and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd).
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- 2021
12. l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells
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David Ortega-Alarcon, Laura Ceballos-Laita, Pawel Botwina, Agnieszka Dabrowska, Olga Abian, Nunzio Iraci, Silvia Moretti, Carmine Ostacolo, Aleksandra Synowiec, Krzysztof Pyrc, Adrián Velázquez-Campoy, Luca Sancineto, Ana Jiménez-Alesanco, Anna Kula-Pacurar, Sonia Vega, Claudio Santi, Sancineto, L., Ostacolo, C., Ortega-Alarcon, D., Jimenez-Alesanco, A., Ceballos-Laita, L., Vega, S., Abian, O., Velazquez-Campoy, A., Moretti, S., Dabrowska, A., Botwina, P., Synowiec, A., Kula-Pacurar, A., Pyrc, K., Iraci, N., Santi, C., Fundación hna, Instituto de Investigación Sanitaria Aragón, Instituto de Salud Carlos III, European Commission, Ministerio de Economía y Competitividad (España), Diputación General de Aragón, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Ministry of Science and Higher Education (Poland), Sancineto, Luca [0000-0002-6199-7399], Ostacolo, Carmine[0000-0003-3715-8680], Ortega-Alarcon, David [0000-0003-1885-4365], Ceballos-Laita, Laura [0000-0002-7223-1719], Abian, Olga [0000-0001-5664-1729], Velázquez-Campoy, Adrián [0000-0001-5702-4538], Moretti, Silvia [0000-0002-8177-7254], Dabrowska, Agnieszka [0000-0003-1499-4950], Botwina, Pawel [0000-0001-9006-1568], Synowiec, Aleksandra [0000-0001-9846-6922], Kula-Pacurar, Anna [0000-0001-8404-2176], Pyrc, Krzysztof [0000-0002-3867-7688], Iraci, Nunzio [0000-0002-1359-8684], Santi, Claudio [0000-0002-7698-8970], Sancineto, Luca, Ostacolo, Carmine, Ortega-Alarcon, David, Ceballos-Laita, Laura, Abian, Olga, Velázquez-Campoy, Adrián, Moretti, Silvia, Dabrowska, Agnieszka, Botwina, Pawel, Synowiec, Aleksandra, Kula-Pacurar, Anna, Pyrc, Krzysztof, Iraci, Nunzio, and Santi, Claudio
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Coronavirus 3C Protease ,Arginine ,Coronavirus disease 2019 (COVID-19) ,Rutin ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,In silico ,Protease Inhibitor ,L-arginine ,Pharmaceutical Science ,Pharmacology ,010402 general chemistry ,Antiviral Agents ,01 natural sciences ,Article ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,QD241-441 ,Pharmacokinetics ,Drug Discovery ,Humans ,Protease Inhibitors ,Physical and Theoretical Chemistry ,Solubility ,l<%2Fspan>-arginine%22">l-arginine ,A549 Cell ,Coronavirus 3C Proteases ,030304 developmental biology ,Antiviral Agent ,0303 health sciences ,SARS-CoV-2 ,Chemistry ,Main protease ,Quercetin ,A549 Cells ,COVID-19 ,Molecular Docking Simulation ,Organic Chemistry ,COVID-19 Drug Treatment ,0104 chemical sciences ,3. Good health ,Chemistry (miscellaneous) ,Molecular Medicine ,Human - Abstract
The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with l-arginine. Tests of the rutin/l-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization., This research was in part founded with POR FESR 2014/2020, and thus, Regione Umbria is gratefully acknowledged (S.M.). This work was supported by Fundación hna (to A.V.-C. and O.A.); Fondo Investiga Covid-19 del Instituto de Investigación Sanitaria de Aragón IIS-A (to O.A. and A.V.-C.); Miguel Servet Program from Instituto de Salud Carlos III (CPII13/00017 to O.A.); Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III and the European Union (ERDF/ESF, ”Investing in your future”) (PI18/00349 to O.A. and a FIS Research Contract to L.C.-L.); Spanish Ministry of Economy and Competitiveness (BFU2016-78232-P to A.V.-C.); Spanish Ministry of Science, Innovation and Universities (FPI Predoctoral Research Contract BES-2017-080739 to D.O.-A.); Diputación General de Aragón (Predoctoral Research Contract 2019 to A.J.-A., ‘Protein Targets and Bioactive Compounds Group’ E45_20R to A.V.-C., ‘Digestive Pathology Group’ B25_20R to O.A.); and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd).This work was supported by the subsidy from the Polish Ministry of Science and Higher Education for research on SARS-CoV-2, a grant from the National Science Center UMO-2017/27/B/NZ6/02488, and EU-Horizon2020 ITN OrganoVir grant 812673 to KP.
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- 2021
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