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

Abstract

Plitidepsin 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 SUMMARY:

Plitidepsin, an inhibitor of SARS-Cov-2 in vitro , is safe and positively influences the outcome of patients hospitalized with COVID-19.

• Authors: José F Varona, Pedro Landete, Jose A Lopez-Martin, Vicente Estrada, Roger Paredes, Pablo Guisado-Vasco, Lucía Fernández de Orueta, Miguel Torralba, Jesús Fortún, Roberto Vates, José Barberán, Bonaventura Clotet, Julio Ancochea, Daniel Carnevali, Noemí Cabello, Lourdes Porras, Paloma Gijón, Alfonso Monereo, Daniel Abad, Sonia Zúñiga, Isabel Sola, Jordi Rodon, Nuria Izquierdo-Useros, Salvador Fudio, María José Pontes, Beatriz de Rivas, Patricia Girón de Velasco, Belén Sopesén, Antonio Nieto, Javier Gómez, Pablo Avilés, Rubin Lubomirov, Kris M White, Romel Rosales, Soner Yildiz, Ann-Kathrin Reuschl, Lucy G Thorne, Clare Jolly, Greg J Towers, Lorena Zuliani-Alvarez, Mehdi Bouhaddou, Kirsten Obernier, Luis Enjuanes, Jose M Fernández-Sousa, Plitidepsin – COVID - 19 Study Group, Nevan J Krogan, José M Jimeno, Adolfo García-Sastre
• Journal: medRxiv : the preprint server for health sciences (medRxiv) (May 25 2021) United States
• PMID: 34075384 (Publication Type: Preprint)