Identification of novel drug targets and screening potential drugs against Cryptococcus gattii: An in silico approach

Robin, Tanjin Barketullah; Rani, Nurul Amin; Ahmed, Nadim; Prome, Anindita Ash; Bappy, Nazmul Islam; Ahmed, Foeaz

doi:10.1016/j.imu.2023.101222

Cited by 6 publications

(2 citation statements)

References 46 publications

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“…To explore the binding affinity between metabolites and proteins, molecular docking, an essential tool for studying interactions between small ligands and large molecules, was employed. The H-DOCK Server (http://hdock.phys.hust.edu.cn/) was chosen for docking PLOS ONE [27], as it provides the necessary tools to discover effective treatments for targeted medicine against deadly pathogens [28]. Furthermore, the CB-Dock server (http://clab.labshare.cn/cbdock/php/blinddock.php) was used to confirm the binding affinity between metabolites and proteins [29].…”

Section: Determining Metabolite and Inhibitor Binding Affinitymentioning

confidence: 99%

Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae

Moin,

Robin,

Patil

et al. 2024

PLoS ONE

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Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae’s infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.

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Section: Determining Metabolite and Inhibitor Binding Affinitymentioning

confidence: 99%

Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae

Moin,

Robin,

Patil

et al. 2024

PLoS ONE

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“…Protein sequence analysis with the BLASTP tool was used to determine the homology of cryptococcal EPSrelated proteins to human proteins and proteins of major fungal pathogens (Candida albicans, Histoplasma capsulatum, and Aspergillus fumigatus) [52][53][54][55][56]. The majority of the analyzed proteins presented very low (<40%) or no homology to proteins found in human cells which indicates them as promising novel anti-fungal drug targets or vaccine antigens [57][58][59]. Among the analyzed proteins 16 presented no significant homology to proteins found in other major fungal pathogens indicating their potential cryptococcus-specific function (Supplementary Table 3).…”

Section: Identification Of Eps-related Proteinsmentioning

confidence: 99%

Proteins associated withCryptococcusspp. extracellular polysaccharides are implicated in virulence, capsule integrity, and biofilm formation

Stempinski,

Jacobs,

Lopes

et al. 2024

Preprint

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Cryptococcus neoformans and Cryptococcus gattii are pathogenic fungi comprising species complexes that are the etiological agents of cryptococcosis. Both fungal species complexes possess a variety of virulence factors that include a polysaccharide capsule, melanin production, enzymes, and the release of polysaccharides. In this study, we characterized the proteins associated with cryptococcal polysaccharides and analyzed their function by studying mutants deficient in their expression. Mass spectrometry analysis of exopolysaccharide fractions revealed 62 proteins, many of which were previously uncharacterized. Analysis of capsule size, structure, and integrity in protein-deficient mutants allowed us to identify four proteins, which we named Extracellular Polysaccharide Related proteins (Exa1-4), and whose absence affected proper capsule assembly and EPS release. In summary, cryptococcal exopolysaccharide is associated with proteins that are implicated in virulence, capsular integrity, and biofilm formation. Our results associated new phenotypes for four previously unknown genes and show that the filtered polysaccharide preparations are a rich source of proteins that can inform capsular assembly, virulence, and immunological studies.

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Subtractive proteomics analysis to uncover the potent drug targets for distinctive drug design of Candida auris

Bappy

Robin

Prome

et al. 2023

Heliyon

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Identification of novel drug targets and screening potential drugs against Cryptococcus gattii: An in silico approach

Cited by 6 publications

References 46 publications

Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae

Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae

Proteins associated withCryptococcusspp. extracellular polysaccharides are implicated in virulence, capsule integrity, and biofilm formation

Subtractive proteomics analysis to uncover the potent drug targets for distinctive drug design of Candida auris

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