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 Varona, Jose F
A1 Landete, Pedro
A1 Lopez-Martin, Jose A
A1 Estrada, Vicente
A1 Paredes, Roger
A1 Guisado-Vasco, Pablo
A1 Fernandez de Orueta, Lucia
A1 Torralba, Miguel
A1 Fortun, Jesus
A1 Vates, Roberto
A1 Barberan, Jose
A1 Clotet, Bonaventura
A1 Ancochea, Julio
A1 Carnevali, Daniel
A1 Cabello, Noemi
A1 Porras, Lourdes
A1 Gijon, Paloma
A1 Monereo, Alfonso
A1 Abad, Daniel
A1 Zuñiga, Sonia
A1 Sola, Isabel
A1 Rodon, Jordi
A1 Vergara-Alert, Julia
A1 Izquierdo-Useros, Nuria
A1 Fudio, Salvador
A1 Pontes, Maria Jose
A1 de Rivas, Beatriz
A1 Giron de Velasco, Patricia
A1 Nieto, Antonio
A1 Gomez, Javier
A1 Aviles, Pablo
A1 Lubomirov, Rubin
A1 Belgrano, Alvaro
A1 Sopesen, Belen
A1 White, Kris M
A1 Rosales, Romel
A1 Yildiz, Soner
A1 Reuschl, Ann-Kathrin
A1 Thorne, Lucy G
A1 Jolly, Clare
A1 Towers, Greg J
A1 Zuliani-Alvarez, Lorena
A1 Bouhaddou, Mehdi
A1 Obernier, Kirsten
A1 McGovern, Briana L
A1 Rodriguez, M Luis
A1 Enjuanes, Luis
A1 Fernandez-Sousa, Jose M
A1 Krogan, Nevan J
A1 Jimeno, Jose M
A1 Garcia-Sastre, Adolfo
YR 2022
UL http://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.