Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization
Author:
Varona José F., Landete Pedro, Lopez-Martin Jose A.ORCID, Estrada Vicente, Paredes Roger, Guisado-Vasco Pablo, de Orueta Lucía Fernández, 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 Sonia, Sola Isabel, Rodon Jordi, Izquierdo-Useros Nuria, 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 Clare, Towers Greg J., Zuliani-Alvarez Lorena, Bouhaddou Mehdi, Obernier Kirsten, Enjuanes Luis, Fernández-Sousa Jose M., Krogan Nevan J., Jimeno José M., García-Sastre Adolfo,
Abstract
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.One-Sentence SummaryPlitidepsin, an inhibitor of SARS-Cov-2 in vitro, is safe and positively influences the outcome of patients hospitalized with COVID-19.
Publisher
Cold Spring Harbor Laboratory
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