In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of Streptococcus mutans through Antigen I/II

• Published in: International journal of molecular sciences 2021-01, Vol.22 (1), p.377
• Main Authors: Rivera-Quiroga, Raúl E., Cardona, Néstor, Padilla, Leonardo, Rivera, Wbeimar, Rocha-Roa, Cristian, Diaz De Rienzo, Mayri A., Morales, Sandra M., Martinez, María C.
• Format: Article
• Language: English
• Subjects: Adhesins; Adhesion; Antigens; Antimicrobial agents; Bacteria; Bacterial proteins; Binding sites; Biofilms; Crystal structure; Cytotoxicity; Dental caries; Dental plaque; Dynamic stability; Fluorides; Microbiota; Molecular dynamics; Oral hygiene; Pathogens; Pellicle; Polystyrene resins; Probiotics; Scanning electron microscopy; Streptococcus infections; Streptococcus mutans; Sucrose
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22010377

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.