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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