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

Varona, J. F.; Landete, P.; Lopez-Martin, J. A.; Estrada, V.; Paredes, R.; Guisado-Vasco, P.; Fernandez de Orueta, L.; Torralba, M.; Fortun, J.; Vates, R.; Barberan, J.; Clotet, B.; Ancochea, J.; Carnevali, D.; Cabello, N.; Porras, L.; Gijon, P.; Monereo, A.; Abad, D.; Zuniga, S.; Sola, I.; Rodon, J.; Izquierdo-Useros, N.; Fudio, S.; Pontes, M. J.; de Rivas, B.; Giron de Velasco, P.; Sopesen, B.; Nieto, A.; Gomez, J.; Aviles, P.; Lubomirov, R.; White, K. M.; Rosales, R.; Yildiz, S.; Reuschl, A.-K.; Thorne, L. G.; Jolly, C.; Towers, G. J.; Zuliani-Alvarez, L.; Bouhaddou, M.; Obernier, K.; Enjua,

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.