Development of targeted degradation of Nuclear Receptor Binding SET Domain Protein 2 (NSD2) by Proteolysis-targeting chimera (PROTAC) for the study of its role in SARS-CoV-2 infections

The recent outbreak of the SARS-CoV-2 associated coronavirus disease, COVID-19, had been declared a global pandemic by the World Health Organization. There is still only a minimal understanding of the virus and an absence of effective targeted therapy for its treatment. Epigenetic regulations in cells control the expression of genes without modifications to the genetic codes itself, and epigenetic-targeted therapy development had been widely proposed as a promising approach to antiviral therapeutics. NSD2 is protein involved in epigenetic control to silence genes and has been reported to be upregulated and known to interact with some key proteins in SARS-CoV-2 infected cells. This project focuses on developing a method to precisely target the degradation of NSD2 via a technique called PROTAC. This could provide a first-in-class method for targeted degradation of NSD2 that could be used to study the protein function and to develop potential therapeutics for COVID-19.

Faculty Supervisor:

Cheryl Arrowsmith;Mathieu Lupien

Student:

Yan David Nie

Partner:

Structural Genomics Consortium

Discipline:

Medicine

Sector:

Professional, scientific and technical services

University:

University of Toronto