Trial reportLife science alliance2022
Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.
Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IMulticenter StudyRandomized Controlled Trial
In one paragraph
Trial report in Life science alliance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04382066 (Multicenter, Randomized, Parallel and Proof of Concept Study to Evaluate the Safety Profile of Three Doses of Plitidepsin in Patients With COVID-19 Requiring Hospitalization), which is not on this map. Cited by 27 papers.
0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.2field-weighted citation impact, top 4% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Multicenter, Randomized, Parallel and Proof of Concept Study to Evaluate the Safety Profile of Three Doses of Plitidepsin in Patients With COVID-19 Requiring Hospitalization
Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- Extending the Targets for Coronavirus Antivirals Beyond That of Approved Drugs: Insights From Preclinical Research.Microbial biotechnology · 2026Review
- Can plitidepsin be used as an antiviral against RSV?mSphere · 2025Article
- Marine-Derived Compounds: A New Horizon in Cancer, Renal, and Metabolic Disease Therapeutics.Marine drugs · 2025Review
- Synthesis and Performance of l-Tryptophanamide and (The Journal of organic chemistry · 2025Article
- Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or mNature communications · 2025Article
- Plitidepsin as an Immunomodulator against Respiratory Viral Infections.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Article
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- Insights for COVID-19 in 2023.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2023Review
- Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art.International journal of molecular sciences · 2023Review
- The Role of Cyclodextrins in COVID-19 Therapy-A Literature Review.International journal of molecular sciences · 2023Review
- A Survey of Didemnin Depsipeptide Production inMarine drugs · 2023Article
- COVID-19: An Overview of SARS-CoV-2 Variants-The Current Vaccines and Drug Development.BioMed research international · 2023Review
- Plitidepsin in adult patients with COVID-19 requiring hospital admission: A long-term follow-up analysis.Frontiers in cellular and infection microbiology · 2023Article
- Recent Advancement in Anticancer Compounds from Marine Organisms: Approval, Use and Bioinformatic Approaches to Predict New Targets.Marine drugs · 2022Review
- Some natural compounds and their analogues having potent anti- SARS-CoV-2 and anti-proteases activities as lead molecules in drug discovery for COVID-19.European journal of medicinal chemistry reports · 2022Review
- Revisiting potential value of antitumor drugs in the treatment of COVID-19.Cell & bioscience · 2022Review
- A comprehensive insight into current control of COVID-19: Immunogenicity, vaccination, and treatment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Investigating the structure-activity relationship of marine polycyclic batzelladine alkaloids as promising inhibitors for SARS-CoV-2 main protease (MComputers in biology and medicine · 2022Article
Corrections and comments
- Update of
Authors and funding
51 authors at 19 institutions in 3 countries.
Jose F VaronaDepartamento de Medicina Interna, Hospital Universitario HM Monteprincipe, HM Hospitales, Madrid, Spain jfvarona@hmhospitales.com.ORCID 0000-0003-4764-9440
Pedro LandeteHospital Universitario La Princesa, Madrid, Spain.
Jose A Lopez-MartinVirology and Inflammation Unit, PharmaMar, SA, Madrid, Spain.ORCID 0000-0001-7530-3207
Vicente EstradaHospital Clínico San Carlos, Madrid, Spain.
Roger ParedesInfectious Diseases Department, IrsiCaixa AIDS Research Institute, Barcelona, Spain.
Pablo Guisado-VascoHospital Universitario Quironsalud Madrid, Madrid, Spain.
Lucia Fernandez de OruetaUniversidad Europea, Madrid, Spain.
Miguel TorralbaHealth Sciences Faculty, University of Alcalá, Madrid, Spain.
Jesus FortunHospital Universitario Ramón y Cajal, Madrid, Spain.ORCID 0000-0002-6959-5263
Roberto VatesInternal Medicine Department, Hospital Universitario de Getafe, Madrid, Spain.
Jose BarberanDepartamento de Medicina Interna, Hospital Universitario HM Monteprincipe, HM Hospitales, Madrid, Spain.
Bonaventura ClotetInfectious Diseases Department, IrsiCaixa AIDS Research Institute, Barcelona, Spain.
Julio AncocheaHospital Universitario La Princesa, Madrid, Spain.ORCID 0000-0001-7451-4133
Daniel CarnevaliHospital Universitario Quironsalud Madrid, Madrid, Spain.
Noemi CabelloInfectious Diseases Department, Clinico San Carlos University Hospital, Madrid, Spain.
Lourdes PorrasInternal Medicine, Hospital General de Ciudad Real, Ciudad Real, Spain.
Paloma GijonClinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Alfonso MonereoInternal Medicine Department, Hospital Universitario de Getafe, Madrid, Spain.
Daniel AbadUniversidad Europea, Madrid, Spain.
Sonia ZuñigaDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.ORCID 0000-0003-2549-6826
Isabel SolaDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
Jordi RodonIRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, Bellaterra, Spain.ORCID 0000-0002-1032-9091
Julia Vergara-AlertIRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la UAB, Bellaterra, Spain.
Nuria Izquierdo-UserosIrsiCaixa AIDS Research Institute, Barcelona, Spain.ORCID 0000-0002-1039-1821
Salvador FudioClinical Pharmacology Unit, PharmaMar, Madrid, Spain.ORCID 0000-0001-7320-6139
Maria Jose PontesMedical Affairs, PharmaMar, Madrid, Spain.
Beatriz de RivasMedical Affairs, PharmaMar, Madrid, Spain.
Patricia Giron de VelascoVirology and Inflammation Unit, PharmaMar, SA, Madrid, Spain.
Antonio NietoBio Statistics Unit, PharmaMar, Madrid, Spain.
Javier GomezBio Statistics Unit, PharmaMar, Madrid, Spain.
Pablo AvilesPreclinical Unit, Pharmamar, Madrid, Spain.
Rubin LubomirovClinical Pharmacology Unit, PharmaMar, Madrid, Spain.
Alvaro BelgranoBio Statistics Unit, PharmaMar, Madrid, Spain.
Belen SopesenVirology and Inflammation Unit, PharmaMar, SA, Madrid, Spain.
Kris M WhiteDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-0889-0506
Romel RosalesDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Soner YildizDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ann-Kathrin ReuschlDivision of Infection and Immunity, University College London, London, UK.
Lucy G ThorneDivision of Infection and Immunity, University College London, London, UK.ORCID 0000-0001-7358-6047
Clare JollyDivision of Infection and Immunity, University College London, London, UK.
Greg J TowersDivision of Infection and Immunity, University College London, London, UK.
Lorena Zuliani-AlvarezQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
Mehdi BouhaddouQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
Kirsten ObernierQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-4025-1299
Briana L McGovernDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-0492-9904
M Luis RodriguezDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Luis EnjuanesDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
Jose M Fernandez-SousaPharmamar, Madrid, Spain.
Nevan J KroganDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-4902-337X
Jose M JimenoVirology and Inflammation Unit, PharmaMar, SA, Madrid, Spain.
Adolfo Garcia-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-6551-1827
PharmaMar (Spain) · ESIcahn School of Medicine at Mount Sinai · USGladstone Institutes · USHospital Universitario de Getafe · ESUniversity College London · GBCentro Nacional de Biotecnología · ESCentre de Recerca en Sanitat Animal · ESHospital Universitario Quirónsalud Madrid · ESIrsiCaixa · ESUniversidad San Pablo CEU · ESHospital Clínico San Carlos · ESHospital General Universitario de Ciudad Real · ESHospital General Universitario Gregorio Marañón · ESHospital Universitario de La Princesa · ESHospital Universitario Ramón y Cajal · ESInstituto de Salud Carlos III · ESUniversidad Complutense de Madrid · ESUniversidad de Alcalá · ESUniversitat de Vic - Universitat Central de Catalunya · ES
Funding
NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00014 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GARCIA-SASTRE, ADOLFO · 2021 to 2025
$62.6MThe role of Listeria cyclic-di-AMP during infection and immunityP01AI063302 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI PORTNOY, DANIEL A · 2004 to 2025
$45.5MSARS-CoV adaptations through a Systems Biology Lens (SYBIL)U19AI135972 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Adolfo Garcia-Sastre · 2018 to 2026
$27.2MTechnology Development Project - Increasing the complexity of ex vivo human airway models for studying immune response to viral infectionU19AI142733 · NIAID · JACKSON LABORATORY · PI Adolfo Garcia-Sastre, Anna Karolina Palucka · 2019 to 2026
$23.1MRESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2018 to 2026
$21.4MX-ray Screening and Rapid Structure DeterminationP50AI150476 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2019 to 2021
$14.4MNovel VP30-host Interactions that Negatively Regulate Ebola Virus InfectionR01AI143292 · NIAID · WASHINGTON UNIVERSITY · PI AMARASINGHE, GAYA K., BASLER, CHRISTOPHER F · 2019 to 2023
$4.0MDiscovery of novel, ubiquitin-regulated mechanisms of TB control by macrophagesR01AI120694 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COX, JEFFERY S, KROGAN, NEVAN J · 2015 to 2019
$3.3MMedical Research Council MR/S023380/1Medical Research Council MR/W005611/1NIAID NIH HHS 75N93021C00014NIAID NIH HHS P01 AI063302NIAID NIH HHS P50 AI150476NIAID NIH HHS R01 AI120694NIAID NIH HHS R01 AI143292NIAID NIH HHS U19 AI135972NIAID NIH HHS U19 AI135990NIAID NIH HHS U19 AI142733
Abstract
Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log
Indexed as
COVID-19 Drug TreatmentAdultAgedCell Line, TumorCOVID-19DepsipeptidesDrug Evaluation, PreclinicalFemaleHospitalizationHumansKaplan-Meier EstimateLength of StayMaleMiddle AgedNeutropeniaPeptides, CyclicDepsipeptidesPeptides, Cyclicplitidepsin
Identifiers
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Read underepoch 390
Registered trials
NCT04382066ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.