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Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization.
Jose F. Varona; Pedro Landete; Jose A Lopez-Martin; Vicente Estrada; Roger Paredes; Pablo Guisado-Vasco; Lucia Fernandez de Orueta; Miguel Torralba; Jesus Fortun; Roberto Vates; Jose Barberan; Bonaventura Clotet; Julio Ancochea; Daniel Carnevali; Noemi Cabello; Lourdes Porras; Paloma Gijon; Alfonso Monereo; Daniel Abad; Sonia Zuñiga; Isabel Sola; Jordi Rodon; Nuria Izquierdo-Useros; Salvador Fudio; Maria Jose Pontes; Beatriz de Rivas; Patricia Giron de Velasco; Belen Sopesen; Antonio Nieto; Javier Gomez; Pablo Aviles; Rubin Lubomirov; Kris M White; Romel Rosales; Soner Yildiz; Ann-Kathrin Reuschl; Lucy G. Thorne; Clare Jolly; Greg J. Towers; Lorena Zuliani-Alvarez; Mehdi Bouhaddou; Kirsten Obernier; Luis Enjuanes; Jose M Fernandez-Sousa; - Plitidepsin COVID Study Group; Nevan J Krogan; Jose M. Jimeno; Adolfo Garcia-Sastre.
Afiliación
  • Jose F. Varona; Departamento de Medicina Interna, Hospital Universitario HM Monteprincipe, HM Hospitales, Madrid, Spain. Facultad de Medicina, Universidad San Pablo-CEU, Madrid
  • Pedro Landete; Hospital Universitario de La Princesa. Madrid, Spain. Universidad Autonoma de Madrid, Madrid, Spain.
  • Jose A Lopez-Martin; PharmaMar. Virology & Inflammation Dept. Colmenar Viejo, Madrid, Spain.
  • Vicente Estrada; Hospital Clinico San Carlos, Madrid, Spain. Universidad Complutense de Madrid, Madrid, Spain.
  • Roger Paredes; IrsiCaixa AIDS Research Institute
  • Pablo Guisado-Vasco; Internal Medicine Department, Hospital Universitario Quironsalud, Madrid, Spain. Universidad Europea, Madrid, Spain.
  • Lucia Fernandez de Orueta; Internal Medicine Department, Hospital Universitario de Getafe, Madrid, Spain. European University of Madrid, Madrid, Spain.
  • Miguel Torralba; Internal Medicine, Guadalajara University Hospital, Guadalajara, Spain. University of Alcala, Madrid, Spain.
  • Jesus Fortun; Hospital Universitario Ramon y Cajal, Madrid, Spain.
  • Roberto Vates; Internal Medicine Department, Hospital Universitario de Getafe, Madrid, Spain.
  • Jose Barberan; Hospital Universitario HM Monteprincipe, Madrid, Spain. Facultad de Medicina San Pablo CEU, Madrid, Spain.
  • Bonaventura Clotet; Head of Infectious Diseases Department, Director of the Research Lab, IrsiCaixa, Barcelone, Spain. Professor of the UAB and the UVIC-UCC, Barcelone, Spain.
  • Julio Ancochea; Hospital Universitario La Princesa, Madrid, Spain. Centro de Investigacion en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII
  • Daniel Carnevali; Hospital Universitario Quironsalud, Madrid, Spain Universidad Europea, Madrid, Spain.
  • Noemi Cabello; Infectious Diseases Department, San Carlos University Hospital. Madrid Spain.
  • Lourdes Porras; Internal Medicine, Hospital General de Ciudad Real, Ciudad Real, Spain.
  • Paloma Gijon; Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañon, Instituto de Investigacion Sanitaria Gregorio Marañon
  • Alfonso Monereo; Internal Medicine Department, Hospital Universitario de Getafe, Madrid, Spain
  • Daniel Abad; Internal Medicine Department, Hospital Universitario de Getafe, Madrid, Spain. European University of Madrid, Madrid, Spain.
  • Sonia Zuñiga; Department of Molecular and Cell Biology, Centro Nacional de Biotecnologia (CNBCSIC), Madrid, Spain.
  • Isabel Sola; Department of Molecular and Cell Biology, Centro Nacional de Biotecnologia (CNBCSIC), Madrid, Spain.
  • Jordi Rodon; IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, Bellaterra, Spain
  • Nuria Izquierdo-Useros; IrsiCaixa AIDS Research Institute, 08916, Badalona, Spain. Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Spain.
  • Salvador Fudio; PharmaMar - Clinical Pharmacology Unit. Colmenar Viejo, Madrid, Spain
  • Maria Jose Pontes; PharmaMar - Medical Affairs Unit. Colmenar Viejo. Madrid, Spain.
  • Beatriz de Rivas; PharmaMar - Medical Affairs Unit. Colmenar Viejo, Madrid, Spain.
  • Patricia Giron de Velasco; PharmaMar. Virology & Inflammation Dept. Colmenar Viejo, Madrid, Spain.
  • Belen Sopesen; PharmaMar. Virology & Inflammation Dept. Colmenar Viejo, Madrid, Spain. Sylentis, S.A.U., Tres Cantos, Madrid, Spain. Biocross, S.L., Valladolid, Spain.
  • Antonio Nieto; PharmaMar - Statistics Unit. Colmenar Viejo, Madrid, Spain.
  • Javier Gomez; PharmaMar - Statistics Unit. Colmenar Viejo, Madrid, Spain.
  • Pablo Aviles; PharmaMar - Preclinical Unit. Colmenar Viejo, Madrid, Spain
  • Rubin Lubomirov; PharmaMar - Clinical Pharmacology Unit. Colmenar Viejo, Madrid, Spain
  • Kris M White; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health Emerging Pathogens Institute, Icahn School of Medicine at
  • Romel Rosales; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health Emerging Pathogens Institute, Icahn School of Medicine at
  • Soner Yildiz; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health Emerging Pathogens Institute, Icahn School of Medicine at
  • Ann-Kathrin Reuschl; Division of Infection and Immunity, University College Londo, London, WC1E 6BT, United Kigdom.
  • Lucy G. Thorne; Division of Infection and Immunity, University College Londo, London, WC1E 6BT, United Kigdom.
  • Clare Jolly; Division of Infection and Immunity, University College Londo, London, WC1E 6BT, United Kigdom.
  • Greg J. Towers; Division of Infection and Immunity, University College Londo, London, WC1E 6BT, United Kigdom
  • Lorena Zuliani-Alvarez; Quantitative Biosciences Institute (QBI), San Francisco, CA 94158, USA. J. David Gladstone Institutes, San Francisco, CA 94158, USA. QBI, Coronavirus Research G
  • Mehdi Bouhaddou; Quantitative Biosciences Institute (QBI), San Francisco, CA 94158, USA. J. David Gladstone Institutes, San Francisco, CA 94158, USA. QBI, Coronavirus Research G
  • Kirsten Obernier; Quantitative Biosciences Institute (QBI), San Francisco, CA 94158, USA. J. David Gladstone Institutes, San Francisco, CA 94158, USA. QBI, Coronavirus Research G
  • Luis Enjuanes; Department of Molecular and Cell Biology, Centro Nacional de Biotecnologia (CNB-CSIC), Madrid, Spain.
  • Jose M Fernandez-Sousa; PharmaMar, S.A., Colmenar Viejo, Madrid, Spain.
  • - Plitidepsin COVID Study Group;
  • Nevan J Krogan; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Quantitative Biosciences Institute (QBI), San Francisco, CA 94158, USA.
  • Jose M. Jimeno; PharmaMar. Virology & Inflammation Dept. Colmenar Viejo, Madrid, Spain.
  • Adolfo Garcia-Sastre; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health Emerging Pathogens Institute, Icahn School of Medicine at
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-21257505
ABSTRACT
Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19. One-Sentence SummaryPlitidepsin, an inhibitor of SARS-Cov-2 in vitro, is safe and positively influences the outcome of patients hospitalized with COVID-19.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Cohort_studies / Experimental_studies / Observational_studies / Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Cohort_studies / Experimental_studies / Observational_studies / Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint