PT  - JOURNAL ARTICLE
AU  - Varona, Jose F
AU  - Landete, Pedro
AU  - Lopez-Martin, Jose A
AU  - Estrada, Vicente
AU  - Paredes, Roger
AU  - Guisado-Vasco, Pablo
AU  - Fernandez de Orueta, Lucia
AU  - Torralba, Miguel
AU  - Fortun, Jesus
AU  - Vates, Roberto
AU  - Barberan, Jose
AU  - Clotet, Bonaventura
AU  - Ancochea, Julio
AU  - Carnevali, Daniel
AU  - Cabello, Noemi
AU  - Porras, Lourdes
AU  - Gijon, Paloma
AU  - Monereo, Alfonso
AU  - Abad, Daniel
AU  - Zuñiga, Sonia
AU  - Sola, Isabel
AU  - Rodon, Jordi
AU  - Vergara-Alert, Julia
AU  - Izquierdo-Useros, Nuria
AU  - Fudio, Salvador
AU  - Pontes, Maria Jose
AU  - de Rivas, Beatriz
AU  - Giron de Velasco, Patricia
AU  - Nieto, Antonio
AU  - Gomez, Javier
AU  - Aviles, Pablo
AU  - Lubomirov, Rubin
AU  - Belgrano, Alvaro
AU  - Sopesen, Belen
AU  - White, Kris M
AU  - Rosales, Romel
AU  - Yildiz, Soner
AU  - Reuschl, Ann-Kathrin
AU  - Thorne, Lucy G
AU  - Jolly, Clare
AU  - Towers, Greg J
AU  - Zuliani-Alvarez, Lorena
AU  - Bouhaddou, Mehdi
AU  - Obernier, Kirsten
AU  - McGovern, Briana L
AU  - Rodriguez, M Luis
AU  - Enjuanes, Luis
AU  - Fernandez-Sousa, Jose M
AU  - Krogan, Nevan J
AU  - Jimeno, Jose M
AU  - Garcia-Sastre, Adolfo
TI  - Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19
AID  - 10.26508/lsa.202101200
DP  - 2022 Apr 01
TA  - Life Science Alliance
PG  - e202101200
VI  - 5
IP  - 4
4099  - http://www.life-science-alliance.org/content/5/4/e202101200.short
4100  - http://www.life-science-alliance.org/content/5/4/e202101200.full
SO  - Life Sci. Alliance2022 Apr 01; 5
AB  - Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.