PT  - JOURNAL ARTICLE
AU  - Jose F Varona
AU  - Pedro Landete
AU  - Jose A Lopez-Martin
AU  - Vicente Estrada
AU  - Roger Paredes
AU  - Pablo Guisado-Vasco
AU  - Lucia Fernandez de Orueta
AU  - Miguel Torralba
AU  - Jesus Fortun
AU  - Roberto Vates
AU  - Jose Barberan
AU  - Bonaventura Clotet
AU  - Julio Ancochea
AU  - Daniel Carnevali
AU  - Noemi Cabello
AU  - Lourdes Porras
AU  - Paloma Gijon
AU  - Alfonso Monereo
AU  - Daniel Abad
AU  - Sonia Zuñiga
AU  - Isabel Sola
AU  - Jordi Rodon
AU  - Julia Vergara-Alert
AU  - Nuria Izquierdo-Useros
AU  - Salvador Fudio
AU  - Maria Jose Pontes
AU  - Beatriz de Rivas
AU  - Patricia Giron de Velasco
AU  - Antonio Nieto
AU  - Javier Gomez
AU  - Pablo Aviles
AU  - Rubin Lubomirov
AU  - Alvaro Belgrano
AU  - Belen Sopesen
AU  - Kris M White
AU  - Romel Rosales
AU  - Soner Yildiz
AU  - Ann-Kathrin Reuschl
AU  - Lucy G Thorne
AU  - Clare Jolly
AU  - Greg J Towers
AU  - Lorena Zuliani-Alvarez
AU  - Mehdi Bouhaddou
AU  - Kirsten Obernier
AU  - Briana L McGovern
AU  - M Luis Rodriguez
AU  - Luis Enjuanes
AU  - Jose M Fernandez-Sousa
AU  - Nevan J Krogan
AU  - Jose M Jimeno
AU  - Adolfo Garcia-Sastre
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  - https://www.life-science-alliance.org/content/5/4/e202101200.short
4100  - https://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.