Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

In silico Selection and in vitro Evaluation of Novel Inhibitors of Streptococcus Mutans Ag I/II Surface Protein

Version 1 : Received: 15 October 2020 / Approved: 16 October 2020 / Online: 16 October 2020 (13:48:43 CEST)

How to cite: Rivera-Quiroga, R.E.; Cardona, N.; Padilla, L.; Rivera, W.; Rocha, C.; Diaz De Rienzo, M.; Morales, S.M.; Martinez, M.C. In silico Selection and in vitro Evaluation of Novel Inhibitors of Streptococcus Mutans Ag I/II Surface Protein. Preprints 2020, 2020100351 (doi: 10.20944/preprints202010.0351.v1). Rivera-Quiroga, R.E.; Cardona, N.; Padilla, L.; Rivera, W.; Rocha, C.; Diaz De Rienzo, M.; Morales, S.M.; Martinez, M.C. In silico Selection and in vitro Evaluation of Novel Inhibitors of Streptococcus Mutans Ag I/II Surface Protein. Preprints 2020, 2020100351 (doi: 10.20944/preprints202010.0351.v1).

Abstract

Streptococcus mutans is well known for having virulence factors associated with its cariogenic role, such as glucosyltransferases, which have been used as targets for the virtual screening of molecules with inhibitory capacity. The Antigen I/II of S. mutans is involved in the adhesion to the surface of the tooth and the bacterial co-aggregation in the biofilm formation, despite that, this protein has not been used as a target in a virtual strategy search for inhibitors. In this study we identified in silico and evaluated in vitro molecules with adhesion inhibitory potential on S. mutans Ag I/II. 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 have found three molecules (ZI-187, ZI-939, ZI-906) that were not cytotoxic and inhibited 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 three new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates and provides a new computational line for the search and selection of safe inhibitory molecules against different pathogens.

Subject Areas

Streptococcus mutans; adhesion proteins; Antigen I/II; Structure-based virtual screening; molecular dynamics

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.