Structure based virtual screening identifies novel competitive inhibitors for the sialoglycan binding protein Hsa

Infective endocarditis (IE) is a cardiovascular disease often caused by bacteria of the group of streptococci, which includes and . Previous research has found that a serine-rich repeat (SRR) proteins on the bacterial surface play a critical role in pathogenesis by facilitating bacterial attachment to sialyated glycans displayed on human platelets. Despite its important role in disease progression, there are currently no anti-adhesive drugs available on the market. Here, we performed structure-based virtual screening using an ensemble docking approach followed by consensus scoring to identify novel inhibitors against the sialoglycan binding domain of the SRR adhesin protein Hsa from the strain DL1. cross screening against the glycan binding domains of closely related SRR proteins from five other or strains was also performed to further reduce false positives. Using our screening strategy we successfully predicted nine compounds which were able to displace the native ligand (sialyl-T antigen) in an assay and bind competitively to adhesin protein Hsa (∼20% hit rate).