Abelson Kinase Inhibitors for the Treatment of SARS-CoV-2

Coronavirus is an enveloped, positive-strand RNA virus. Under the electron microscope, the coronavirus has coronal protrusions at the edges and looks like a crown, so it is called a coronavirus. Novel coronavirus (SARS-CoV-2) is an emerging coronavirus considered as one of the major public threats with a total number of 28,120 confirmed cases and 564 associated deaths reported by China as of January 2020. However, there is currently a lack of vaccines or antivirals to treat SARS-CoV-2.

Since the SARS outbreak in 2003 and the MERS outbreak in 2012, professional virologists at Creative Biolabs have been exploring antiviral drugs for a long time and have accumulated rich experience. At present, our coronavirus research team is working on the development of small molecule inhibitors, especially small molecule kinase inhibitors. These inhibitors have been found to be effective against coronavirus infection in vitro.

What is Abelson (Abl) Kinase?

AbI kinase is a reversible non-receptor tyrosine kinase and belongs to the cytoplasmic member of the ABL subfamily (protein tyrosine kinase family enzymes). AbI kinase can be activated by a variety of stimuli, thereby regulating a variety of cellular pathways, including cell migration, adhesion, and actin reorganization. Moreover, Abl family kinases Abl1 and Abl2 regulate a variety of cellular processes during development and normal homeostasis. Studies have shown that their functions can be destroyed by the pathological processes of inflammation, cancer and viral infection.

Fig.1 Schematics of the functional domains in Abl. (Stefania, 2014)

Rationale for Abl Kinase Inhibitors as Potent Inhibitors of SARS-CoV-2

Studies have shown that Abl inhibitors can inhibit SARS-CoV and MERS-CoV, which further indicate the importance of the Abl pathway in coronavirus replication. Imatinib mesylate, another Abl inhibitor, has been shown to prevent the release of Ebola and poxviruses and the entry of coxsackie virus. These data suggest that the Abl pathway may be important for the replication of many different virus families. Therefore, inhibitors of Abl pathway have great potential to be broad-spectrum antiviral drugs.

Given the importance of Abl in viral infections, specific inhibitors against Abl kinase have been sought to treat viral infections. Currently, Creative Biolabs is committed to developing Abl kinase inhibitors for the treatment of SARS-CoV-2.

Fig.2 The MOA of ABL kinase inhibitors – Imatinib.

One-Stop Small Drug Discovery Services

With state-of-art computer-aided drug development platforms and advanced technologies, Creative Biolabs is capable of offering end-to-end small molecule durg development service. We utilize leading informatics, virtual screening and molecular modeling techniques to help our clients identify new hits, and support their leading chemistry optimization programs. For each drug discovery program, our team is committed to providing our client with a final complete plan within 1 year before entering the IND phase.

For more detailed information, please feel free to contact us or directly send us an inquiry.

Explore more through the following publications:

• Coleman, C. M., Sisk, J. M., Mingo, R. M., Nelson, E. A., White, J. M., & Frieman, M. B. (2016). Abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus fusion. Journal of virology, 90(19), 8924-8933.
• Coleman, C. M., Sisk, J. M., Mingo, R. M., Nelson, E. A., White, J. M., & Frieman, M. B. (2016). ABL kinase inhibitors are potent inhibitors of SARS-CoV and MERS-CoV fusion. Journal of Virology.

Reference

1. Gonfloni, S., et al. Defying c-Abl signaling circuits through small allosteric compounds. Frontiers in genetics, 2014. 5, 392.

For Research Use Only. We do not provide direct services or products for patients.