Imatinib is not a potent anti-SARS-CoV-2 drug

Helong Zhao, Michelle Mendenhall, Michael W. Deininger

10.1038/s41375-020-01045-9

Other curated

Abstract

Imatinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI) used to treat chronic myeloid leukemia (CML), was reported to inhibit infection of SARS-CoV, the coronavirus responsible for the 2003 SARS outbreak, and MERS-CoV, the cause of Middle East Respiratory Syndrome, in cell culture assays [1,2,3]. Mechanistic studies suggested that SARS-CoV relies on ABL2 kinase activity to infect host cells and that inhibiting ABL2 with imatinib blocks coronavirus entry via preventing viral fusion with the cell membrane [1, 2]. Since the SARS-CoV-2 genome is ~80% homologous to that of SARS-CoV [4] and both viruses use host cell ACE2 protein as receptors [5], it is plausible that imatinib also has anti-SARS-CoV-2 activity. Moreover, imatinib was identified as a leading hit from a large-scale drug screening for SARS-CoV-2 protease inhibitors using the Reframe library of clinical and near-clinical compounds [6]. These data suggest that imatinib may have anti-SARS-CoV-2 activity, either on-target through inhibition of ABL1/2 or off-target through a previously unrecognized protease-inhibiting effect. Although the precise mechanism remains unclear, these data provide a rationale for testing imatinib as an antiviral against COVID-19 in clinical trials. Three prospective randomized clinical trials are underway to study the therapeutic efficacy of imatinib vs. standard of care or placebo in patients with COVID-19, including NCT04357613 (France), NCT04394416 (USA), and EudraCT2020-001236-10 (The Netherlands). However, the anti-SARS-CoV-2 efficacy of imatinib in a standard viral replication assay has not been demonstrated.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Imatinib	Imatinib mesylate, Gleevec