title: In silico identification of potential inhibitors targeting Streptococcus mutans sortase A.
abstract: Dental caries is one of the most common chronic diseases and is caused by acid fermentation of bacteria adhered to the teeth. Streptococcus mutans (S. mutans) utilizes sortase A (SrtA) to anchor surface proteins to the cell wall and forms a biofilm to facilitate its adhesion to the tooth surface. Some plant natural products, especially several flavonoids, are effective inhibitors of SrtA. However, given the limited number of inhibitors and the development of drug resistance, the discovery of new inhibitors is urgent. Here, the high-throughput virtual screening approach was performed to identify new potential inhibitors of S. mutans SrtA. Two libraries were used for screening, and nine compounds that had the lowest scores were chosen for further molecular dynamics simulation, binding free energy analysis and absorption, distribution, metabolism, excretion and toxicity (ADMET) properties analysis. The results revealed that several similar compounds composed of benzofuran, thiadiazole and pyrrole, which exhibited good affinities and appropriate pharmacokinetic parameters, were potential inhibitors to impede the catalysis of SrtA. In addition, the carbonyl of these compounds can have a key role in the inhibition mechanism. These findings can provide a new strategy for microbial infection disease therapy.
authors.affiliation: School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment, Sichuan University, Chengdu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.affiliation: School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment, Sichuan University, Chengdu, China.
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Liang
authors.affiliation: School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment, Sichuan University, Chengdu, China.
authors.forename: Min-Yue
authors.initials: MY
authors.lastname: Bao
authors.affiliation: School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment, Sichuan University, Chengdu, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Sun
authors.affiliation: School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment, Sichuan University, Chengdu, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.affiliation: School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment, Sichuan University, Chengdu, China.
authors.forename: Jian-Zong
authors.initials: JZ
authors.lastname: Li
authors.affiliation: School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment, Sichuan University, Chengdu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment, Sichuan University, Chengdu, China.
authors.forename: Kai-Min
authors.initials: KM
authors.lastname: Lu
authors.affiliation: School of Life Sciences and Key Laboratory of Ministry of Education for Bio-Resources and Bio-Environment, Sichuan University, Chengdu, China.|State Key Laboratory of Biotherapy/Collaborative Innovation Centre for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.|State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Jin-Ku
authors.initials: JK
authors.lastname: Bao
mesh_terms: D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors*; D001422:Bacterial Adhesion / Q000187:drug effects*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001572:Benzofurans / Q000494:pharmacology*; D018441:Biofilms; D003198:Computer Simulation; D003546:Cysteine Endopeptidases; D003731:Dental Caries / Q000382:microbiology*; D011758:Pyrroles / Q000494:pharmacology*; D013295:Streptococcus mutans / Q000201:enzymology*; D013830:Thiadiazoles / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D001572:Benzofurans; D011758:Pyrroles; D013830:Thiadiazoles; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases; C105430:benzofuran