Virtual screening for potential inhibitors of β(1,3)-D-glucan synthase as drug candidates against fungal cell wall

Zinat Farhadi; Tayebeh Farhadi; Seyed MohammadReza Hashemian

doi:10.1080/21556660.2020.1734010

Virtual screening for potential inhibitors of β(1,3)-D-glucan synthase as drug candidates against fungal cell wall

J Drug Assess. 2020 Mar 11;9(1):52-59. doi: 10.1080/21556660.2020.1734010. eCollection 2020.

Authors

Zinat Farhadi^{1

2

3}, Tayebeh Farhadi¹, Seyed MohammadReza Hashemian^{1

4}

Affiliations

¹ Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Behavioral Disease Counseling Center, Marvdasht Health Center, Shiraz University of Medical Sciences, Shiraz, Iran.
³ Department of Microbiology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
⁴ Critical Care Department, Farhikhtegan Hospital, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.

Abstract

Background: To enhance the outcome in patients with invasive candidiasis, initiation of an efficient antifungal treatment in a suitable dosage is necessary. Echinocandins (e.g. caspofungin) inhibit the enzyme β(1,3)-D-glucan synthase of the fungal cell wall. Compared to azoles and other antifungal agents, echinocandins have lower adverse effects and toxicity in humans. Echinocandins are available in injectable (intravenous) form. Methods: In this study, to identify the novel oral drug-like compounds that affect the fungal cell wall, downloaded oral drug-like compounds from the ZINC database were processed with a virtual screening procedure. The docking free energies were calculated and compared with the known inhibitor caspofungin. Four molecules were selected as the most potent ligands and subjected to hydrogen bonds analysis. Results: Considering the hydrogen bond analysis, two compounds (ZINC71336662 and ZINC40910772) were predicted to better interact with the active site of β(1,3)-D-glucan synthase compared with caspofungin. Conclusion: The introduced compound in this study may be valuable to analyze experimentally as a novel oral drug candidate targeting fungal cell walls.

Keywords: Candidiasis; caspofungin; oral drug; virtual screening; β(1,3)-D-glucan synthase.