Gaining molecular insights towards inhibition of foodborne fungi Aspergillus fumigatus by a food colourant violacein via computational approach

Abstract Filamentous Fungal Human Pathogens (FFHPs) such as Aspergillus fumigatus, are growing resistant to currently available antifungal drugs. One possible target, the Nucleoside diphosphate kinase (Ndk) is significant for nucleotide biosynthesis and crucial for fungal metabolism. Violacein, a na...

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Main Authors: R. Sindhu, Smitha S. Bhat, Jiraporn Sangta, Chandan Dharmashekar, Bhargav Shreevatsa, Chandan Shivamallu, Devananda Devegowda, Shiva Prasad Kollur, Sheikh F. Ahmad, Sabry M. Attia, Sarana Rose Sommano, Shashanka K. Prasad
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-81471-2
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author R. Sindhu
Smitha S. Bhat
Jiraporn Sangta
Chandan Dharmashekar
Bhargav Shreevatsa
Chandan Shivamallu
Devananda Devegowda
Shiva Prasad Kollur
Sheikh F. Ahmad
Sabry M. Attia
Sarana Rose Sommano
Shashanka K. Prasad
author_facet R. Sindhu
Smitha S. Bhat
Jiraporn Sangta
Chandan Dharmashekar
Bhargav Shreevatsa
Chandan Shivamallu
Devananda Devegowda
Shiva Prasad Kollur
Sheikh F. Ahmad
Sabry M. Attia
Sarana Rose Sommano
Shashanka K. Prasad
author_sort R. Sindhu
collection DOAJ
description Abstract Filamentous Fungal Human Pathogens (FFHPs) such as Aspergillus fumigatus, are growing resistant to currently available antifungal drugs. One possible target, the Nucleoside diphosphate kinase (Ndk) is significant for nucleotide biosynthesis and crucial for fungal metabolism. Violacein, a natural food colorant, was examined for its antifungal effects against Aspergillus fumigatus via computational approach against the Ndk protein. Known and predicted interactions of Ndk with proteins was performed using the STRING application. Molecular docking was performed using Schrodinger Maestro software (V.14.1) under enhanced precision docking, with OPLS4 forcefield. MDS was performed for 500ns under OPLS4 forcefield and the TIP3P solvent system. The geometry optimization for DFT was performed using the Becke 3-parameter exchange functional (B3LYP) method. The Molecular Docking Studies revealed significant interactions with good binding energy between Violacein and Ndk. Subsequent MD Simulations confirmed the stability of Violacein-Ndk complex, compared to the reference ligand-complex, indicating a stable interaction between the protein and violacein. The energy band gap of violacein was found to be 0.072567 eV suggesting its softness with lower kinetic stability and higher chemical reactivity. The results suggest Violacein could potentially disrupt nucleotide metabolism by targeting Ndk, thus demonstrating antifungal activity. However, further experimental validation is required to confirm these computational findings and explore the practical use of Violacein in antifungal treatments.
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spelling doaj-art-8b60aa5e8a4d4d8480c36db58eea3ebd2025-08-20T02:20:41ZengNature PortfolioScientific Reports2045-23222024-12-0114111710.1038/s41598-024-81471-2Gaining molecular insights towards inhibition of foodborne fungi Aspergillus fumigatus by a food colourant violacein via computational approachR. Sindhu0Smitha S. Bhat1Jiraporn Sangta2Chandan Dharmashekar3Bhargav Shreevatsa4Chandan Shivamallu5Devananda Devegowda6Shiva Prasad Kollur7Sheikh F. Ahmad8Sabry M. Attia9Sarana Rose Sommano10Shashanka K. Prasad11Department of Microbiology, JSS Academy of Higher Education & ResearchDepartment of Biotechnology and Bioinformatics, JSS Academy of Higher Education & ResearchInterdisciplinary Program in Biotechnology, Graduate School, Chiang Mai UniversityDepartment of Microbiology, JSS Academy of Higher Education & ResearchDepartment of Microbiology, JSS Academy of Higher Education & ResearchDepartment of Biotechnology and Bioinformatics, JSS Academy of Higher Education & ResearchCentre of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSSAHER)School of Physical Sciences, Amrita Vishwa VidyapeethamDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityPlant Bioactive Compound Laboratory, Faculty of Agriculture, Chiang Mai UniversityDepartment of Biotechnology and Bioinformatics, JSS Academy of Higher Education & ResearchAbstract Filamentous Fungal Human Pathogens (FFHPs) such as Aspergillus fumigatus, are growing resistant to currently available antifungal drugs. One possible target, the Nucleoside diphosphate kinase (Ndk) is significant for nucleotide biosynthesis and crucial for fungal metabolism. Violacein, a natural food colorant, was examined for its antifungal effects against Aspergillus fumigatus via computational approach against the Ndk protein. Known and predicted interactions of Ndk with proteins was performed using the STRING application. Molecular docking was performed using Schrodinger Maestro software (V.14.1) under enhanced precision docking, with OPLS4 forcefield. MDS was performed for 500ns under OPLS4 forcefield and the TIP3P solvent system. The geometry optimization for DFT was performed using the Becke 3-parameter exchange functional (B3LYP) method. The Molecular Docking Studies revealed significant interactions with good binding energy between Violacein and Ndk. Subsequent MD Simulations confirmed the stability of Violacein-Ndk complex, compared to the reference ligand-complex, indicating a stable interaction between the protein and violacein. The energy band gap of violacein was found to be 0.072567 eV suggesting its softness with lower kinetic stability and higher chemical reactivity. The results suggest Violacein could potentially disrupt nucleotide metabolism by targeting Ndk, thus demonstrating antifungal activity. However, further experimental validation is required to confirm these computational findings and explore the practical use of Violacein in antifungal treatments.https://doi.org/10.1038/s41598-024-81471-2Aspergillus fumigatusViolaceinAntifungalFFHPNucleoside diphosphate kinaseFood colourant
spellingShingle R. Sindhu
Smitha S. Bhat
Jiraporn Sangta
Chandan Dharmashekar
Bhargav Shreevatsa
Chandan Shivamallu
Devananda Devegowda
Shiva Prasad Kollur
Sheikh F. Ahmad
Sabry M. Attia
Sarana Rose Sommano
Shashanka K. Prasad
Gaining molecular insights towards inhibition of foodborne fungi Aspergillus fumigatus by a food colourant violacein via computational approach
Scientific Reports
Aspergillus fumigatus
Violacein
Antifungal
FFHP
Nucleoside diphosphate kinase
Food colourant
title Gaining molecular insights towards inhibition of foodborne fungi Aspergillus fumigatus by a food colourant violacein via computational approach
title_full Gaining molecular insights towards inhibition of foodborne fungi Aspergillus fumigatus by a food colourant violacein via computational approach
title_fullStr Gaining molecular insights towards inhibition of foodborne fungi Aspergillus fumigatus by a food colourant violacein via computational approach
title_full_unstemmed Gaining molecular insights towards inhibition of foodborne fungi Aspergillus fumigatus by a food colourant violacein via computational approach
title_short Gaining molecular insights towards inhibition of foodborne fungi Aspergillus fumigatus by a food colourant violacein via computational approach
title_sort gaining molecular insights towards inhibition of foodborne fungi aspergillus fumigatus by a food colourant violacein via computational approach
topic Aspergillus fumigatus
Violacein
Antifungal
FFHP
Nucleoside diphosphate kinase
Food colourant
url https://doi.org/10.1038/s41598-024-81471-2
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