Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization.
| Autor: | Varona JF, Landete P, Lopez-Martin JA, Estrada V, Paredes R, Guisado-Vasco P, de Orueta LF, Torralba M, Fortún J, Vates R, Barberán J, Clotet B, Ancochea J, Carnevali D, Cabello N, Porras L, Gijón P, Monereo A, Abad D, Zúñiga S, Sola I, Rodon J, Izquierdo-Useros N, Fudio S, Pontes MJ, de Rivas B, Girón de Velasco P, Sopesén B, Nieto A, Gómez J, Avilés P, Lubomirov R, White KM, Rosales R, Yildiz S, Reuschl AK, Thorne LG, Jolly C, Towers GJ, Zuliani-Alvarez L, Bouhaddou M, Obernier K, Enjuanes L, Fernández-Sousa JM, Krogan NJ, Jimeno JM, García-Sastre A |
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| Jazyk: | angličtina |
| Zdroj: | MedRxiv : the preprint server for health sciences [medRxiv] 2021 May 25. Date of Electronic Publication: 2021 May 25. |
| DOI: | 10.1101/2021.05.25.21257505 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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