S. pyogenes is a gram-positive human pathogen that has been linked to various diseases from skin infections to necrotizing fasciitis and rheumatic heart disease. The orphan protein tyrosine phosphatase from S. pyogenes (SP-PTP) was recently identified as a major virulence regulator, with studies showing that the knockdown of SP-PTP leads to reduced growth, impaired cell division, and decreased ability to invade host cells, exhibiting its importance in S. pyogenes pathogenesis. This makes it a viable target for new antibiotics, specifically targeting bacterial virulence. This project aims to identify small-molecule inhibitors of SP-PTP. An available crystal structure of SP-PTP shows high similarity with other low molecular weight PTPs (LMWPTPs). Using this structure, computational analysis of potential druggable pockets was performed. Consensus pockets were identified using FTMap and DoGSite and further validated by molecular dynamics druggability simulations. A virtual screening of a panel of FDA-approved drugs was also performed targeting these pockets.
