CCAB-sponsored Mitacs fellowship leads to novel potential anti-viral treatments
For the past couple of years, Dr. Wei Zhang, a CCAB-sponsored Mitacs Elevate fellow and the recipient of the 2016 Mitacs Outstanding Innovation (postdoctoral fellow) award, has been leading a project to engineer variants of the small protein ubiquitin as potential novel anti-viral compounds.
First designed in Dr. Sachdev Sidhu’s laboratory, Ubv technology consists of screening phage-displayed libraries of ubiquitin variants (Ubvs) against a ubiquitin-binding target of interest to obtain Ubvs that have high affinity and specificity for the target. By displacing wild type ubiquitin from the target, the Ubv can modulate its function. Given the increasingly recognized role of ubiquitin in biological processes, Dr. Sidhu’s group first focused on generating Ubvs for many enzymes of the human Ubiquitin Proteasome System.
During his MITACS fellowship, Dr. Zhang applied Ubv technology to create anti-viral compounds by targeting viral ubiquitin-binding enzymes. The study, recently published in PLoS Pathogens, was a collaboration of Dr. Sidhu’s group (University of Toronto) with viral biology experts Dr. Marjolein Kikkert (Leiden University Medical Center) and Dr. Brian Mark (University of Manitoba). Many viruses encode deubiquitinases (DUBs, enzymes that remove ubiquitin from proteins) that are crucial for viral replication and pathogenicity. Dr. Zhang generated Ubvs that specifically bind DUBs of the MERS virus and inhibit their function. The study demonstrates that the Ubvs can act as potent anti-viral agents. Once coupled to an efficient delivery system, Ubvs could thus become novel effective drugs against many viruses that depend on ubiquitin-binding enzymes.
Read a news feature on this story on the Donnelly Centre website.