Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2
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 pa...
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| Veröffentlicht in: | Antiviral research 2021-09, Vol.193, p.105137-105137, Article 105137 |
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| creator | Touret, Franck Driouich, Jean-Sélim Cochin, Maxime Petit, Paul Rémi Gilles, Magali Barthélémy, Karine Moureau, Grégory Mahon, Francois-Xavier Malvy, Denis Solas, Caroline de Lamballerie, Xavier Nougairède, Antoine |
| description | 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.
•Imatinib and masitinib inhibit SARS-CoV-2 replication in VeroE6.•Imatinib does not block SARS-CoV-2 replication in human bronchial airway epithelia.•Imatinib does not exhibit antiviral activity in a golden Syrian hamster model despite a good lung impregnation. |
| doi_str_mv | 10.1016/j.antiviral.2021.105137 |
| format | Article |
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•Imatinib and masitinib inhibit SARS-CoV-2 replication in VeroE6.•Imatinib does not block SARS-CoV-2 replication in human bronchial airway epithelia.•Imatinib does not exhibit antiviral activity in a golden Syrian hamster model despite a good lung impregnation.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2021.105137</identifier><identifier>PMID: 34265358</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Antiviral Agents - pharmacology ; Antivirals ; Cell Line ; Chlorocebus aethiops ; Coronavirus ; Covid-19 ; COVID-19 - epidemiology ; COVID-19 - virology ; COVID-19 Drug Treatment ; Drug Evaluation, Preclinical ; Drug Repositioning ; Enzyme Inhibitors - pharmacology ; Epithelium ; Female ; Humans ; Imatinib ; Imatinib Mesylate - pharmacology ; Life Sciences ; Lung - pathology ; Male ; Mesocricetus ; Santé publique et épidémiologie ; SARS-CoV-2 ; SARS-CoV-2 - drug effects ; Tyrosine kinase inhibitor ; Vero Cells ; Virus Replication - drug effects</subject><ispartof>Antiviral research, 2021-09, Vol.193, p.105137-105137, Article 105137</ispartof><rights>2021 The Authors</rights><rights>Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.</rights><rights>Attribution - NonCommercial - NoDerivatives</rights><rights>2021 The Authors 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-b2e82056921aecea4d7b1929f29beda0d3a9308226a9ef23f0c2031733ba5ff33</citedby><cites>FETCH-LOGICAL-c509t-b2e82056921aecea4d7b1929f29beda0d3a9308226a9ef23f0c2031733ba5ff33</cites><orcidid>0000-0002-4743-3626 ; 0000-0002-4734-2249 ; 0000-0002-0943-9648 ; 0000-0003-1292-9573 ; 0000-0003-2318-9662 ; 0000-0001-7895-2720</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.antiviral.2021.105137$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34265358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03328717$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Touret, Franck</creatorcontrib><creatorcontrib>Driouich, Jean-Sélim</creatorcontrib><creatorcontrib>Cochin, Maxime</creatorcontrib><creatorcontrib>Petit, Paul Rémi</creatorcontrib><creatorcontrib>Gilles, Magali</creatorcontrib><creatorcontrib>Barthélémy, Karine</creatorcontrib><creatorcontrib>Moureau, Grégory</creatorcontrib><creatorcontrib>Mahon, Francois-Xavier</creatorcontrib><creatorcontrib>Malvy, Denis</creatorcontrib><creatorcontrib>Solas, Caroline</creatorcontrib><creatorcontrib>de Lamballerie, Xavier</creatorcontrib><creatorcontrib>Nougairède, Antoine</creatorcontrib><title>Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description>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.
•Imatinib and masitinib inhibit SARS-CoV-2 replication in VeroE6.•Imatinib does not block SARS-CoV-2 replication in human bronchial airway epithelia.•Imatinib does not exhibit antiviral activity in a golden Syrian hamster model despite a good lung impregnation.</description><subject>Animals</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antivirals</subject><subject>Cell Line</subject><subject>Chlorocebus aethiops</subject><subject>Coronavirus</subject><subject>Covid-19</subject><subject>COVID-19 - epidemiology</subject><subject>COVID-19 - virology</subject><subject>COVID-19 Drug Treatment</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug Repositioning</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Epithelium</subject><subject>Female</subject><subject>Humans</subject><subject>Imatinib</subject><subject>Imatinib Mesylate - pharmacology</subject><subject>Life Sciences</subject><subject>Lung - pathology</subject><subject>Male</subject><subject>Mesocricetus</subject><subject>Santé publique et épidémiologie</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV-2 - drug effects</subject><subject>Tyrosine kinase inhibitor</subject><subject>Vero Cells</subject><subject>Virus Replication - drug effects</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2P0zAQhiMEYsvCXwAf4ZBij5M4viBVFbArVQKxwNVynEnXVWoX24nEv8dVlgq4IB9sjZ955-MtileMrhllzdvDWrtkZxv0uAYKLEdrxsWjYsVaAaWksnlcrDLZlLyu4Kp4FuOBUtoI2T4trngFTc3rdlWYzwHNaJ01eiQ463HSyXpH_EBuj_npbEd6j5E4n0icTicfErEpkiki0ZFoRy6dkD5Me6L32rqYyN3my1259d9LeF48GfQY8cXDfV18-_D-6_am3H36eLvd7EpTU5nKDrAFWjcSmEaDuupFxyTIAWSHvaY915LTFqDREgfgAzVAOROcd7oeBs6vi3eL7mnqjtgbdCl3pU7BHnX4qby26u8fZ-_V3s-qBVGBEFngzSJw_0_azWanzjHKObSCiZll9vVDseB_TBiTOtpocBy1Qz9FBXUNss2nyqhYUBN8jAGHizaj6mynOqjLEtXZTrXYmTNf_jnRJe-3fxnYLADmvc4Wg4rGojPY2-xrUr23_y3yC-u3tf8</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Touret, Franck</creator><creator>Driouich, Jean-Sélim</creator><creator>Cochin, Maxime</creator><creator>Petit, Paul Rémi</creator><creator>Gilles, Magali</creator><creator>Barthélémy, Karine</creator><creator>Moureau, Grégory</creator><creator>Mahon, Francois-Xavier</creator><creator>Malvy, Denis</creator><creator>Solas, Caroline</creator><creator>de Lamballerie, Xavier</creator><creator>Nougairède, Antoine</creator><general>Elsevier B.V</general><general>Elsevier Masson</general><general>The Authors. 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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.
•Imatinib and masitinib inhibit SARS-CoV-2 replication in VeroE6.•Imatinib does not block SARS-CoV-2 replication in human bronchial airway epithelia.•Imatinib does not exhibit antiviral activity in a golden Syrian hamster model despite a good lung impregnation.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34265358</pmid><doi>10.1016/j.antiviral.2021.105137</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-4743-3626</orcidid><orcidid>https://orcid.org/0000-0002-4734-2249</orcidid><orcidid>https://orcid.org/0000-0002-0943-9648</orcidid><orcidid>https://orcid.org/0000-0003-1292-9573</orcidid><orcidid>https://orcid.org/0000-0003-2318-9662</orcidid><orcidid>https://orcid.org/0000-0001-7895-2720</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Antiviral Agents - pharmacology Antivirals Cell Line Chlorocebus aethiops Coronavirus Covid-19 COVID-19 - epidemiology COVID-19 - virology COVID-19 Drug Treatment Drug Evaluation, Preclinical Drug Repositioning Enzyme Inhibitors - pharmacology Epithelium Female Humans Imatinib Imatinib Mesylate - pharmacology Life Sciences Lung - pathology Male Mesocricetus Santé publique et épidémiologie SARS-CoV-2 SARS-CoV-2 - drug effects Tyrosine kinase inhibitor Vero Cells Virus Replication - drug effects |
| title | Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2 |
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