Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (ScreenIT)
Abstract
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.
Article activity feed
-
SciScore for 10.1101/2020.11.17.386904: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: All samples purchased from Epithelix SARL have been obtained with informed consent.
IRB: These studies were conducted according to the declaration of Helsinki on biomedical research (Hong Kong amendment, 1989), and received approval from local ethics committee.
IACUC: In vivo experiments: In vivo experiments were approved by the local ethical committee (C2EA—14) and the French ‘Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation’ (APAFIS#23975) and performed in accordance with the French national guidelines and the European legislation covering the use of animals for scientific purposes.Randomization not detected. Blinding not detected. P… SciScore for 10.1101/2020.11.17.386904: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: All samples purchased from Epithelix SARL have been obtained with informed consent.
IRB: These studies were conducted according to the declaration of Helsinki on biomedical research (Hong Kong amendment, 1989), and received approval from local ethics committee.
IACUC: In vivo experiments: In vivo experiments were approved by the local ethical committee (C2EA—14) and the French ‘Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation’ (APAFIS#23975) and performed in accordance with the French national guidelines and the European legislation covering the use of animals for scientific purposes.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable For the first HAE experiment, epithelium derived from a 56-year-old donor Caucasian female with no existing pathologies reported or detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cell line: VeroE6 (ATCC CRL-1586) cells were grown in minimal essential medium (Life Technologies) with 7⍰5% heat-inactivated fetal calf serum (FCS; Life Technologies), at 37°C with 5% CO2 with 1% penicillin/streptomycin (PS, 5000U.mL−1 and 5000µg.mL−1 respectively; Life Technologies) and supplemented with 1⍰% non-essential amino acids (Life Technologies). VeroE6suggested: NoneSoftware and Algorithms Sentences Resources All data obtained were analyzed using GraphPad Prism 7 software (Graphpad software) GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Statistical analysis: Graphical representations and statistical analyses were performed with Graphpad Prism 7 (Graphpad software). Graphpadsuggested: (GraphPad, RRID:SCR_000306)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
-
