Molecular docking and pharmacokinetic evaluation of natural compounds as targeted inhibitors against Crz1 protein in Rhizoctonia solani.

Arshi Malik,Mohammed Tarique,Waleed N Hassan,Ayed Dera,Rana Noor,Sarah Afaq,Mohamed Abd Ellatif,Basiouny El-Gamal

doi:10.6026/97320630015277

Arshi Malik, Mohammed Tarique + Show 6 more

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https://doi.org/10.6026/97320630015277

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Abstract

Crz1p regulates Calcineurin, a serine-threonine-specific protein phosphatase, in Rhizoctonia solani. It has attracted consideration as a novel target of antifungal therapy based on studies in numerous pathogenic fungi, including, Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus. To investigate whether Calcineurin can be a useful target for the treatment of Crz1 protein in R. solani causing wet root rot in Chickpea. The work presented here reports the in-silico studies of Crz1 protein against natural compounds. This study Comprises of quantitative structure-toxicity relationship (QSTR) and quantitative structure-activity relationship (QSAR). All compounds showed high binding energy for Crz1 protein through molecular docking. Further, a pharmacokinetic study revealed that these compounds had minimal side effects. Biological activity spectrum prediction of these compounds showed potential antifungal properties by showing significant interaction with Crz1. Hence, these compounds can be used for the prevention and treatment of wet root rot in Chickpea.

Highlights

Calcineurin is essential for cell viability under specific environmental conditions [1]
Calcineurin has attracted contemplation as a novel target of antifungal therapy based on previous studies in various fungi, e.g. C. neoformans, C. albicans and A. fumigates [6,7,8,9,10]
It is of interest to study natural compounds as targeted inhibitors against Crz1 protein in R. solani causing wet root rot in Chickpea

Summary

Introduction

Calcineurin is essential for cell viability under specific environmental conditions [1]. Calcineurin is a heterodimer of a catalytic subunit (genes of CNA1 and CNA2) and a regulatory subunit (CNB1) [2]. Calcineurin deficient cells (CNA1, CNA2, and CNB1) failed to grow in the presence of Na+/Li+, Mn2+, alkaline pH, and lose viability in prolonged incubation with mating pheromone [3]. All of these environments, as well as the addition of Ca2+ to the growth medium, encourage Ca2+/ calcineurindependent gene expression [3, 4]. Many of the physiological functions of calcineurin in Rhizoctonia solani are mediated by its regulation of Crz1p. Very little is known about the calcineurin pathway in Rhizoctonia solani

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