High-Throughput assay for TMPRSS2 inhibitor screening, based on human extracellular vesicles containing active and stable TMPRSS2 (EVZYM)
The University of Antwerp has developed and validated a screening assay for TMPRSS2 (transmembrane protease S1 member 2) inhibition, based on the use of human extracellular vesicles containing active TMPRSS2. The assay is suitable for high-throughput screening at partner’s site or smaller scale screening at UAntwerp.
Situation before
TMPRSS2 is a protease involved in human infections by viral pathogens such as coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV2) and certain strains of influenza-viruses. TMPRSS2 therefore represents a highly promising therapeutic target in infectious diseases. Despite its attractive therapeutic profile, obtaining high-quality TMPRSS2 preparations (i.e. displaying good and desirable activity profiles) through recombinant methods has proven to be highly inefficient and quite troublesome. To the best of our knowledge, no high-quality, active TMPRSS2 preparations are commercially available today. Therefore, a readily available assay based on a native source of TMPRSS2 with high activity is of value for parties that develop drugs targeting TMPRSS2.
Technology
The EVZYM technology provides a novel in vitro screening method for identifying compounds as transmembrane protease S1 member 2 (TMPRSS2) inhibitors. It is based on human extracellular vesicles (EVs) containing native, enzymatically active TMPRSS2. The method is applicable as high throughput assay and is fully validated and ready to implement.
We provide a 384-well plate end-point fluorometric assay with a signal to blank ratio (S/B) above 10 and a substrate conversion < 10 % to avoid saturation of the target protease and substrate inhibition. Coefficients of Variation (CV) are below 5 %. Z’, a measure to quantify the suitability of the assay for use in a full-scale HTS, is 0.91. DMSO is tolerated up to 5 % and methanol up to 2.5 %. The assay can be run at room temperature or at 37 °C.
Partners we search for
We are looking for pharma/biotech partners or academic groups that are looking for a readily available source of human, natural, enzymatically active TMPRSS2 as well as those who are looking for a TMPRSS2 validated inhibition assay. The technology is Patent pending.
About the researchers/research group
The UAntwerp Laboratory of Medical Biochemistry, founded by Prof. S. Scharpé, studies the structure-function relationship of proteins with a medical relevance in human pathologies. Its main expertise lies in protein biochemistry, ranging from protein production, functional and cellular assays (contact Prof. De Meester) towards protein biophysics and crystallography-based structure determination (contact Prof. Y. Sterckx). The lab has a longstanding collaboration with the Medicinal Chemistry group and participated in many academic and industrial collaborations on drug development, among others in the DPP4 and FAP inhibitor area. The lab belongs to the research Consortium of Excellence Infla-Med (www.uantwerpen.be/infla-med).
More information
University of Antwerp
Valorisation Office
Middelheimlaan 1
2020 Antwerpen
Phone: +32 3 265 19 84