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Updated: Dec 9, 2025
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Structure based virtual screening identifies small molecule effectors for the sialoglycan binding protein Hsa
Rupesh Agarwal1,2, Barbara A Bensing3, Dehui Mi4
1UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6309, U.S.A.
Insights
Researchers identified novel small molecules that inhibit Streptococcus gordonii
Area of Science:
- Microbiology
- Cardiovascular Diseases
- Drug Discovery
Background:
- Infective endocarditis (IE) is a serious cardiovascular disease often caused by viridans group streptococci.
- Serine-rich repeat (SRR) proteins on bacteria like Streptococcus gordonii are crucial for attaching to human platelets, aiding disease progression.
- Current treatments lack anti-adhesive drugs targeting this bacterial attachment mechanism.
Purpose of the Study:
- To identify novel small molecules that can inhibit the Hsa adhesin protein from Streptococcus gordonii.
- To find potential anti-infective agents that block bacterial adhesion to human platelets.
Main Methods:
- Structure-based virtual screening using ensemble docking and consensus scoring was employed.
- In vitro assays were used to test the ability of identified compounds to displace the native ligand (sialyl-T antigen).
- Hierarchical clustering based on MACCS fingerprints was used to analyze the chemical diversity of the identified compounds.
Main Results:
- Nine compounds were identified that successfully displaced the native ligand and competitively bind to the Hsa adhesin.
- Eight of the identified compounds possess novel chemical scaffolds, distinct from the native ligand.
- The study demonstrates that SRR adhesins can be targeted by diverse small molecules.
Conclusions:
- Small molecules can effectively inhibit SRR adhesin proteins, preventing bacterial adhesion.
- This research opens new pathways for developing anti-infective drugs against infective endocarditis.
- Targeting bacterial adhesins offers a promising strategy for novel therapeutic interventions.
Abstract:
Infective endocarditis (IE) is a cardiovascular disease often caused by bacteria of the viridans group of streptococci, which includes Streptococcus gordonii and Streptococcus sanguinis. Previous research has found that serine-rich repeat (SRR) proteins on the S. gordonii bacterial surface play a critical role in pathogenesis by facilitating bacterial attachment to sialylated glycans displayed on human platelets. Despite their 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 small molecule effectors against the sialoglycan binding domain of the SRR adhesin protein Hsa from the S. gordonii strain DL1. The screening successfully predicted nine compounds which were able to displace the native ligand (sialyl-T antigen) in an in vitro assay and bind competitively to Hsa. Furthermore, hierarchical clustering based on the MACCS fingerprints showed that eight of these small molecules do not share a common scaffold with the native ligand. This study indicates that SRR family of adhesin proteins can be inhibited by diverse small molecules and thus prevent the interaction of the protein with the sialoglycans. This opens new avenues for discovering potential drugs against IE.
