Development of Novel Heterobifunctional Degraders and Antifungal Agents

This thesis explores distinct but overlapping approaches to contemporary drug discovery. PROTAC drugs are an emerging therapeutic approach where molecules hijack the ubiquitin-proteasome system to degrade disease-implicated proteins. Fragment-based and structure-based drug design principles were applied to develop PROTACs targeting two target proteins − BRD4, a prominent cancer target and Mpro, a critical enzyme for SARS-CoV-2 replication. Mpro-degrading PROTACs were developed that may provide a new paradigm for drug development against SARS-CoV-2 and other viral infectious diseases. Lastly, the concept of phenotypic drug discovery and open-source research was enacted for the development of novel antifungal agents.