In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of <i>Streptococcus mutants</i> through Antigen I/II

Eduardo Rivera Quiroga, Raul; Cardona, Nestor; Padilla, Leonardo; Rivera, Wbeimar; C., Rocha-Roa,; Alejandra Diaz De Rienzo, Mayri; Milena Morales Uchima, Sandra; C. Martinez, María

Abstract

Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted; cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates.

Citation

Eduardo Rivera Quiroga, R., Cardona, N., Padilla, L., Rivera, W., C., R.-R., Alejandra Diaz De Rienzo, M., … C. Martinez, M. (2020). In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutants through Antigen I/II. International Journal of Molecular Sciences, 22(1), https://doi.org/10.3390/ijms22010377

• Journal Article Type: Article
• Publication Date: Dec 31, 2020
• Deposit Date: Aug 24, 2023
• Publicly Available Date: Aug 29, 2023
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: 1
• DOI: https://doi.org/10.3390/ijms22010377