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Title

Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization

AuthorsVarona, José F.; Landete, Pedro; López-Martín, José A.; Estrada, Vicente; Paredes, Roger; Guisado Vasco, P.; Fernández de Orueta, Lucía; Torralba, Miguel; Fortún, Jesús; Vates, Roberto; Barberán, José; Clotet, Bonaventura; Ancochea, Julio; Carnevali, Daniel; Cabello, Noemí; Porras, Lourdes; Gijón, Paloma; Monereo, Alfonso; Abad, Daniel; Zúñiga Lucas, Sonia CSIC ORCID ; Solá Gurpegui, Isabel ; Rodón, Jordi; Izquierdo-Useros, Núria; Fudio, Salvador; Pontes, María José; Rivas, Beatriz de; Girón de Velasco, Patricia; Sopesén, Belén; Nieto, Antonio; Gómez, Javier; Avilés, Pablo; Lubomirov, Rubin; White, Kris M.; Rosales, Romel; Yildiz, Soner; Reuschl, Ann-Kathrin; Thorne, Lucy G.; Jolly, Claire; Towers, Greg J.; Zuliani-Alvarez, Lorena; Bouhaddou, Mehdi; Obernier, Kirsten; Enjuanes Sánchez, Luis CSIC ORCID ; Fernández-Sousa, José M.; Plitidepsin – COVID - 19 Study Group; Krogan, Nevan J.; Jimeno, José M.; García-Sastre, Adolfo
KeywordsCOVID-19 treatment
Plitidepsin
eEF1A
SARS-CoV-2
Issue Date25-May-2021
PublisherMedRxiv
CitationMedRxiv: 10.1101/2021.05.25.21257505 (2021)
AbstractPlitidepsin 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.
Publisher version (URL)https://doi.org/10.1101/2021.05.25.21257505
URIhttp://hdl.handle.net/10261/242948
DOI10.1101/2021.05.25.21257505
Appears in Collections:(VICYT) Colección Especial COVID-19
(CNB) Artículos

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