ArticleScience (New York, N.Y.)2021
Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A.
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Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers.
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201citing papers in PubMed
20.9field-weighted citation impact, top 1% of its field
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Who cites it
201 citing papers in PubMed, 362 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
- Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.Life science alliance · 2022Trial
- SARS-CoV-2 nucleocapsid protein hijacks host transcription by targeting eEF1A1.Life science alliance · 2026Article
- Targeting eEF1A1 With Baicalein to Block eEF1A1/Prdx4 Interaction for Treating Sepsis-Mediated Lung Injury.Exploration (Beijing, China) · 2026Article
- Discovery and mutasynthetic optimization of ansatrienin B: A new broad-spectrum inhibitor against RNA viruses.Acta pharmaceutica Sinica. B · 2026Article
- Broad-acting antivirals: the pursuit of pan-viral therapeutics in the era of pandemics.Journal of virology · 2026Review
- Article
- Extending the Targets for Coronavirus Antivirals Beyond That of Approved Drugs: Insights From Preclinical Research.Microbial biotechnology · 2026Review
- Identification of boholamide A analogue as a potential hypoxia-selective anti-triple-negative breast cancer agent by targeting eEF1A1.Acta pharmaceutica Sinica. B · 2026Article
- Broad-spectrum antiviral activity of antisense oligonucleotides targeting GBF1 against SARS-CoV-2 and influenza viruses.iScience · 2026Article
- Geodiamolide A, a Marine Sponge Depsipeptide, Halts Proliferation and Triggers Cell Death in Squamous Cell Carcinoma (A431, NMSC) In Vitro.International journal of molecular sciences · 2026Article
- Paraisariamides: Cycloheptapeptide Toxins from Entomopathogenic Fungi (Journal of natural products · 2026Article
- Can plitidepsin be used as an antiviral against RSV?mSphere · 2025Article
- Article
- Homoharringtonine is highly effective against SARS-CoV-2: a potential first-line defense in future coronavirus epidemics.National science review · 2025Article
- Large Library Docking and Biophysical Analysis of Small-Molecule TMPRSS2 Inhibitors.Journal of medicinal chemistry · 2025Article
- Human protein synthesis requires aminoacyl-tRNA pivoting during proofreading.Nature communications · 2025Article
- Deep learning in the discovery of antiviral peptides and peptidomimetics: databases and prediction tools.Molecular diversity · 2025Review
- Multifaceted Marine Peptides and Their Therapeutic Potential.Marine drugs · 2025Review
- Open-science discovery of DNDI-6510, a compound that addresses genotoxic and metabolic liabilities of the COVID Moonshot SARS-CoV-2 Mpro lead inhibitor.bioRxiv : the preprint server for biology · 2025Article
141 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 8 institutions in 3 countries.
Kris M White *Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. kris.white@mssm.edu nevan.krogan@ucsf.edu adolfo.garcia-sastre@mssm.edu.ORCID https://orcid.org/0000-0003-0889-0506
Romel Rosales *Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0001-5326-4753
Soner YildizDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0002-7235-6108
Thomas KehrerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0002-6433-0098
Lisa MiorinDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0003-0989-3178
Elena MorenoDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0002-2301-4558
Sonia JangraDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Melissa B UccelliniDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0003-2589-4824
Raveen RathnasingheDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0002-1260-2493
Lynda CoughlanDepartment of Microbiology and Immunology and Center for Vaccine Development and Global Health (CVD), University of Maryland School of Medicine, Baltimore, MD, USA.ORCID https://orcid.org/0000-0001-9880-6560
Carles Martinez-RomeroDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0001-8888-7715
Jyoti BatraQuantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.ORCID https://orcid.org/0000-0002-2335-0607
Ajda RojcQuantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.ORCID https://orcid.org/0000-0002-6183-7109
Mehdi BouhaddouQuantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.ORCID https://orcid.org/0000-0002-9526-1427
Jacqueline M FabiusQuantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.
Kirsten ObernierQuantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.ORCID https://orcid.org/0000-0002-4025-1299
Marion DejosezHuffington Foundation Center for Cell-Based Research in Parkinson's Disease, Department of Cell, Developmental, and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0002-1360-3260
María José GuillénResearch and Development Department, PharmaMar, 28770 Colmenar Viejo, Madrid, Spain.
Alejandro LosadaResearch and Development Department, PharmaMar, 28770 Colmenar Viejo, Madrid, Spain.
Pablo AvilésResearch and Development Department, PharmaMar, 28770 Colmenar Viejo, Madrid, Spain.
Michael SchotsaertDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0003-3156-3132
Thomas ZwakaHuffington Foundation Center for Cell-Based Research in Parkinson's Disease, Department of Cell, Developmental, and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID https://orcid.org/0000-0002-9271-2456
Marco VignuzziViral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 75724 Paris Cedex 15, France.ORCID https://orcid.org/0000-0002-4400-771X
Kevan M ShokatQuantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.ORCID https://orcid.org/0000-0001-8590-7741
Nevan J KroganDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. kris.white@mssm.edu nevan.krogan@ucsf.edu adolfo.garcia-sastre@mssm.edu.ORCID https://orcid.org/0000-0003-4902-337X
Adolfo García-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. kris.white@mssm.edu nevan.krogan@ucsf.edu adolfo.garcia-sastre@mssm.edu.ORCID https://orcid.org/0000-0002-6551-1827
Icahn School of Medicine at Mount Sinai · USGladstone Institutes · USPharmaMar (Spain) · ESNew York Stem Cell Foundation · USCentre National de la Recherche Scientifique · FRHoward Hughes Medical Institute · USUniversity of California, San Francisco · USUniversity of Maryland, Baltimore · US
Funding
The role of Listeria cyclic-di-AMP during infection and immunityP01AI063302 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI VANCE, RUSSELL E · 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
$27.2MRESEARCH 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 EMERMAN, MICHAEL · 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
$3.3MDecoding the Chlamydia inclusion membrane protein-host protein interactomeR01AI122747 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ENGEL, JOANNE N., KAAKE, ROBYN MIDORI · 2016 to 2020
$3.1MCombined adjuvant approaches for enhancement of SARS-CoV-2 vaccine efficacyR01AI160706 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCHOTSAERT, MICHAEL, WONG, PAMELA TINMOI · 2022 to 2025
$2.9MImproving the efficacy of mTOR inhibitionR01CA221969 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FAN, QI WEN, SHOKAT, KEVAN M. · 2018 to 2022
$2.9MInhibitors of the G protein GNAS which drives pancreatic tumorigenesisR01CA244550 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHOKAT, KEVAN M. · 2020 to 2024
$2.0MExperimental and natural SARS-CoV-2 infection of the human pancreasR01DK130425 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HOMANN, DIRK, SCHOTSAERT, MICHAEL · 2021 to 2023
$1.3MSystematic Targeting of Oncogene Interacting Proteins to Reveal New Therapeutic StrategiesF32CA239333 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOUHADDOU, MEHDI · 2019 to 2021
$192kNCI NIH HHS F32 CA239333NCI NIH HHS R01 CA221969NCI NIH HHS R01 CA244550NIAID NIH HHS HHSN272201400008CNIAID NIH HHS P01 AI063302NIAID NIH HHS P50 AI150476NIAID NIH HHS R01 AI120694NIAID NIH HHS R01 AI122747NIAID NIH HHS R01 AI143292NIAID NIH HHS R01 AI160706NIAID NIH HHS U19 AI135972NIAID NIH HHS U19 AI135990NIDDK NIH HHS R01 DK130425
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of translation have potent antiviral effects. We found that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (90% inhibitory concentration = 0.88 nM) that is more potent than remdesivir against SARS-CoV-2 in vitro by a factor of 27.5, with limited toxicity in cell culture. Through the use of a drug-resistant mutant, we show that the antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known target eEF1A (eukaryotic translation elongation factor 1A). We demonstrate the in vivo efficacy of plitidepsin treatment in two mouse models of SARS-CoV-2 infection with a reduction of viral replication in the lungs by two orders of magnitude using prophylactic treatment. Our results indicate that plitidepsin is a promising therapeutic candidate for COVID-19.
Indexed as
COVID-19 Drug TreatmentAdenosine MonophosphateAlanineAnimalsAntiviral AgentsCoronavirus Nucleocapsid ProteinsCOVID-19DepsipeptidesDrug Evaluation, PreclinicalFemaleHEK293 CellsHumansLungMiceMice, Inbred C57BLMutationAdenosine MonophosphateAlanineAntiviral AgentsCoronavirus Nucleocapsid ProteinsDepsipeptidesEEF1A1 protein, humannucleocapsid phosphoprotein, SARS-CoV-2Peptide Elongation Factor 1Peptides, CyclicPhosphoproteinsplitidepsinremdesivirRNA, Viral
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