Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2.
Animals
Antiviral Agents
/ pharmacology
COVID-19
/ epidemiology
Cell Line
Chlorocebus aethiops
Drug Evaluation, Preclinical
Drug Repositioning
Enzyme Inhibitors
/ pharmacology
Epithelium
Female
Humans
Imatinib Mesylate
/ pharmacology
Lung
/ pathology
Male
Mesocricetus
SARS-CoV-2
/ drug effects
Vero Cells
Virus Replication
/ drug effects
COVID-19 Drug Treatment
Antivirals
Coronavirus
Covid-19
Imatinib
SARS-CoV-2
Tyrosine kinase inhibitor
Journal
Antiviral research
ISSN: 1872-9096
Titre abrégé: Antiviral Res
Pays: Netherlands
ID NLM: 8109699
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
17
11
2020
revised:
06
07
2021
accepted:
07
07
2021
pubmed:
16
7
2021
medline:
19
8
2021
entrez:
15
7
2021
Statut:
ppublish
Résumé
Following the emergence of SARS-CoV-2, the search for an effective and rapidly available treatment was initiated worldwide based on repurposing of available drugs. Previous reports described the antiviral activity of certain tyrosine kinase inhibitors (TKIs) targeting the Abelson kinase 2 against pathogenic coronaviruses. Imatinib, one of them, has more than twenty years of safe utilization for the treatment of hematological malignancies. In this context, Imatinib was rapidly evaluated in clinical trials against Covid-19. Here, we present the pre-clinical evaluation of imatinib in multiple models. Our results indicated that imatinib and another TKI, the masitinib, exhibit an antiviral activity in VeroE6 cells. However, imatinib was inactive in a reconstructed bronchial human airway epithelium model. In vivo, imatinib therapy failed to impair SARS-CoV-2 replication in a golden Syrian hamster model despite high concentrations in plasma and in the lung. Overall, these results do not support the use of imatinib and similar TKIs as antivirals in the treatment of Covid-19.
Identifiants
pubmed: 34265358
pii: S0166-3542(21)00127-3
doi: 10.1016/j.antiviral.2021.105137
pmc: PMC8274277
pii:
doi:
Substances chimiques
Antiviral Agents
0
Enzyme Inhibitors
0
Imatinib Mesylate
8A1O1M485B
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105137Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
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