RT Journal Article
SR Electronic
T1 Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101200
DO 10.26508/lsa.202101200
VO 5
IS 4
A1 Jose F Varona
A1 Pedro Landete
A1 Jose A Lopez-Martin
A1 Vicente Estrada
A1 Roger Paredes
A1 Pablo Guisado-Vasco
A1 Lucia Fernandez de Orueta
A1 Miguel Torralba
A1 Jesus Fortun
A1 Roberto Vates
A1 Jose Barberan
A1 Bonaventura Clotet
A1 Julio Ancochea
A1 Daniel Carnevali
A1 Noemi Cabello
A1 Lourdes Porras
A1 Paloma Gijon
A1 Alfonso Monereo
A1 Daniel Abad
A1 Sonia Zuñiga
A1 Isabel Sola
A1 Jordi Rodon
A1 Julia Vergara-Alert
A1 Nuria Izquierdo-Useros
A1 Salvador Fudio
A1 Maria Jose Pontes
A1 Beatriz de Rivas
A1 Patricia Giron de Velasco
A1 Antonio Nieto
A1 Javier Gomez
A1 Pablo Aviles
A1 Rubin Lubomirov
A1 Alvaro Belgrano
A1 Belen Sopesen
A1 Kris M White
A1 Romel Rosales
A1 Soner Yildiz
A1 Ann-Kathrin Reuschl
A1 Lucy G Thorne
A1 Clare Jolly
A1 Greg J Towers
A1 Lorena Zuliani-Alvarez
A1 Mehdi Bouhaddou
A1 Kirsten Obernier
A1 Briana L McGovern
A1 M Luis Rodriguez
A1 Luis Enjuanes
A1 Jose M Fernandez-Sousa
A1 Nevan J Krogan
A1 Jose M Jimeno
A1 Adolfo Garcia-Sastre
YR 2022
UL https://www.life-science-alliance.org/content/5/4/e202101200.abstract
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.