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Article - Human and Animal Health • Braz. arch. biol. technol. 64 • 2021 • https://doi.org/10.1590/1678-4324-2021200402   copy

In Silico Screening of DNA Gyrase B Potent Flavonoids for the Treatment of Clostridium difficile Infection from PhytoHub Database

Authorship SCIMAGO INSTITUTIONS RANKINGS

HIGHLIGHTS

Flavonoids potentially target GyrB.

Screened flavonoids have good bioavailability and no toxicity.

Flavonoids could preferentially interact with GyrB and some of them exhibit higher binding affinity towards GyrB than novobiocin.

Abstract

Clostridium difficile infection (CDI) is the most common hospital acquired diarrheal disease with its increasing incidence and mortality rate globally. DNA Gyrase B (GyrB) is a key component of DNA replication process across all bacterial genera; thus, this offers a potential target for the treatment of CDI. In the present study, several virtual screening approaches were employed to identify a novel C. difficile GyrB inhibitor. The 139 known metabolites were screened out from the 480 flavonoids in PhytoHub database. Molinspiration and PROTOX II servers were used to calculate the ADME properties and oral toxicity of the metabolites, whereas mutagenicity, tumorigenicity, irritant, and reproductive effect were predicted using DataWarrior program. The binding mode and the binding efficiency of the screened flavonoids against the GyrB were studied using FlexX docking program. From virtual screening of 139 metabolites, we found 25 flavonoids with no mutagenicity, tumorigenicity, irritant, and reproductive effect. Docking study suggested that flavonoids 1030 ((-)-epicatechin 3'-O-sulfate), 1032 ((-)-epicatechin 4'-O-sulfate), 1049 (3'-O-methyl-(-)-epicatechin 4-O-sulfate), 1051 (3'-O-methyl-(-)-epicatechin 7-O-sulfate), 1055 (4'-O-methyl-(-)-epicatechin 7-O-sulfate) and 1317 (quercetin sulfate) have significantly higher binding affinity than the known GyrB inhibitor novobiocin. The results from molecular dynamics simulation and free energy calculations based on solvated interaction energy suggested that (-)-epicatechin 3'-O-sulfate could be a potential drug candidate in the management of CDI.

Keywords:
Clostridium difficile infection; Virtual screening; ADMET

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