Development and targeting of transcriptional regulatory network controlling FLU1 activation in Candida albicans for novel antifungals

•FLU1 (Major Facilitator Superfamily transporter) has vital role in azole resistance.•We developed a network of TFs for understanding the regulation of FLU1.•9 Antifungals significantly docking with transcription factor (TF) GCN4.•These antifungals have also shown promising result in ADMET studies.•This in silico study gives a platform to improve therapeutics against resistance.

Candidiasis caused by primarily Candida albicans poses serious threat due to dry pipeline and ineffective antifungal strategy against resistance. In this study we propose to target genes involved in efflux mediated Multi drug resistance. The main objective of this study was to understand the regulatory interactions responsible for activating a major MFS transporter gene of Candida albicans. Another aim was to identify the docking effect of certain antifungal compounds upon the transcription factor effectively controlling FLU1. The in silico study carried out here aims at control of gene expression at initial levels. This approach helps to understand regulatory control of FLU1 based on which a predictive map was generated. This data focused on factors with major control that could be suitable target for antifungal agents. The docking results confirm the agreeable effect on the target transcription factor. Broadly this sort of study would account for understanding and targeting any significant gene which in turn would help in adjusting therapeutics accordingly. Further in silico ADMET analysis reported positive values that are indicative of a good antifungal compound with respect to pharmacokinetics. These tests are essential in assessment of good drug candidates because they not only help in refining better drug candidates but weeding out the unsuitable ones too.

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