Imatinib Inhibitors for the Treatment of SARS-CoV-2

The outbreak of a novel coronavirus (SARS-CoV-2), which began in Wuhan, China, has spread rapidly and has now been confirmed in multiple countries. Current epidemiological data indicate that the number of deaths is rapidly increasing. Notably, there are no known therapies for the treatment of SARS-CoV-2. Therefore, there is an urgent need for developing anti-SARS-CoV-2 drugs.

Empowered by decades of research experience in SARS-CoV in 2003 and the MERS-CoV in 2012, Creative Biolabs has built specific knowledge in the fields of virology, epidemiology. At present, our virologists have sufficient evidence to speculate that Abelson kinase inhibitor - imatinib has great potential and is expected to be the next drug candidate for SARS-CoV-2.

Introduction of Imatinib

Imatinib, a tyrosine kinase inhibitor, is also known as "Gleevec" or "Glivec". The inhibitor was approved by the FDA in May 2001 to treat certain types of cancer, such as chronic myelogenous leukemia (CML). Encouraged by the success of imatinib in treating CML patients, scientists have explored its role in other cancers and discovered that imatinib has a similar miraculous effect in gastrointestinal stromal tumors (GIST) and many others malignant tumors, where tyrosine kinases are overexpressed. It is the first member of a new class of drugs that works by inhibiting specific tyrosine kinases rather than non-specifically inhibiting rapidly dividing cells.

Mechanism of imatinib in cancer.Fig.1 Mechanism of imatinib in cancer.

Rationale of Imatinib as Potent Inhibitors for SARS-CoV-2

Imatinib mesylate is a known inhibitor of the Abelson murine leukemia virus oncogene 1 (ABL1) pathway. The ABL1 pathway is known to be a signaling pathway involved in cell differentiation, cell adhesion, and cell stress response. Multiple studies have shown that the ABL1 pathway is important for replicating many different virus families, including SARS-CoV-2. Naturally, imatinib inhibitors have the potential to become broad-spectrum antivirals for the treatment of SARS-CoV-2.

Mechanism of action of Imatinib in virus infectionFig.2 Mechanism of action of imatinib in virus infection.

The following data further demonstrate the importance of the ABL1 inhibitor imatinib in coronavirus replication. Fig. 3 shows that imatinib mesylate is active on both MERS-CoV and SARS-CoV by inhibiting the kinase signaling pathway. Imatinib leads to the formation of six hydrogen-bonded ABL kinase domains by directly inhibiting ABL kinase activity. It inhibits ABL's ability to transfer phosphate groups to tyrosine residues on the substrate, thereby preventing activation of subsequent proliferation signals.

Antiviral activity of imatinibFig.3 Antiviral activity of imatinib mesylate in SARS-CoV and MERS-CoV.( Dyall, 2014)

End-to-end Drug Discovery Services

Creative Biolabs is capable of offering one-stop small molecule drug development service. Empowered by state-of-art computer-aided drug development platform and extensive knowledge in virology, our small drug services range from target identification, structure determination, to biological analysis and synthetic chemistry. For each program, our drug development team is committed to providing our client with a final complete plan within 1 year before entering the IND phase.

Imatinib Inhibitors for The Treatment of SARS-CoV-2

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  1. G Dyall, J., et al. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrobial agents and chemotherapy, 2014. 58(8), pp.4885-4893.
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