Discovery of inhibitors of BK polyomavirus

PROJECT SUMMARY Novel inhibitors of BK polyomavirus BKPyV are urgently needed to prevent the occurrence of virus induced nephropathy allograft failure and hemorrhagic cystitis following transplantation The objective of this Phase I SBIR feasibility study is to identify drug like compounds that specifically inhibit BKPyV replication During the course of this Phase I funding period we will execute a hit finding campaign with a library of compounds with optimal drug like properties Quality hits that emerge from the assay will be subjected to follow on testing that will investigate the potency selectivity and mechanism of action The most interesting of these compounds will be subjected to medicinal chemistry driven hit to lead efforts to explore structure activity relationships SAR The overall goal of this project is to discover one or more novel lead series which is defined as a chemotype inhibitor that demonstrates tractable SAR potent antiviral activity against the available BKPyV strains and minimal cytotoxicity Success in these endeavors will trigger the submission of a Phase II application that will advance the program from Early Lead Optimization through to Candidate Selection Project Narrative Novel therapies with potent and selective activity against BK polyomavirus BKPyV are urgently needed to prevent BK induced nephropathy BKVN ureteral stenosis and hemorrhagic cystitis in immunosuppressed individuals following transplantation We propose to execute an innovative high throughput screening campaign This screen is expected to yield novel compounds targeting BKPyV replication that will serve as starting points for medicinal chemistry hit to lead efforts If successful we will deliver one or more new lead series targeting BKPyV infection