Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.
Adult
Aged
COVID-19
/ virology
Cell Line, Tumor
Depsipeptides
/ adverse effects
Drug Evaluation, Preclinical
/ methods
Female
Hospitalization
/ statistics & numerical data
Humans
Kaplan-Meier Estimate
Length of Stay
/ statistics & numerical data
Male
Middle Aged
Neutropenia
/ chemically induced
Peptides, Cyclic
/ adverse effects
SARS-CoV-2
/ drug effects
Treatment Outcome
Viral Load
/ drug effects
COVID-19 Drug Treatment
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
18
08
2021
revised:
24
12
2021
accepted:
28
12
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
27
1
2022
Statut:
epublish
Résumé
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 log
Identifiants
pubmed: 35012962
pii: 5/4/e202101200
doi: 10.26508/lsa.202101200
pmc: PMC8761492
pii:
doi:
Substances chimiques
Depsipeptides
0
Peptides, Cyclic
0
plitidepsin
Y76ID234HW
Banques de données
ClinicalTrials.gov
['NCT04382066']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : U19 AI142733
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120694
Pays : United States
Organisme : Medical Research Council
ID : MR/W005611/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U19 AI135990
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI063302
Pays : United States
Organisme : NIAID NIH HHS
ID : P50 AI150476
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143292
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93021C00014
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2022 Varona et al.
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