Homology Modeling of Alpha-Glucosidase from Candida albicans: Sequence Analysis and Structural Validation Studies in silico

Rashid, Haroon; Bolzani, Vanderlan da Silva; Khan, Khalid Mohammed; Dutra, Luiz; Ahmad, Nasir; Wadood, Abdul

doi:10.21577/0103-5053.20230123

“…The Ramachandran Plot Assessment (RAMPAGE) server was used to evaluate the quality of 3D structure [ 37 ]. PROCHCK further validated the model.…”

Section: Methodsmentioning

confidence: 99%

Multi-epitopes vaccine design for surface glycoprotein against SARS-CoV-2 using immunoinformatic approach

Arshad,

Rehana,

Saleem

et al. 2024

Heliyon

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“…In the realm of structural protein design and functional investigation, homology modeling stands out as a prominent method. This approach involves predicting the three-dimensional structure of a target protein sequence by aligning it with a known protein template, enabling a comprehensive understanding of protein structures and functions 19 . Alphafold2, an advanced protein structure prediction method, leverages deep learning algorithms and evolutionary conservation principles 20 .…”

Section: Model Building and Validationmentioning

confidence: 99%

Mitigating candidiasis with acarbose by targeting Candida albicans α-glucosidase: in-silico, in-vitro and transcriptomic approaches

David,

Vasudevan,

Solomon

2024

Sci Rep

0

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Biofilm-associated candidiasis poses a significant challenge in clinical settings due to the limited effectiveness of existing antifungal treatments. The challenges include increased pathogen virulence, multi-drug resistance, and inadequate penetration of antimicrobials into biofilm structures. One potential solution to this problem involves the development of novel drugs that can modulate fungal virulence and biofilm formation, which is essential for pathogenesis. Resistance in Candida albicans is initiated by morphological changes from yeast to hyphal form. This transition triggers a series of events such as cell wall elongation, increased adhesion, invasion of host tissues, pathogenicity, biofilm formation, and the initiation of an immune response. The cell wall is a critical interface for interactions with host cells, primarily through various cell wall proteins, particularly mannoproteins. Thus, cell wall proteins and enzymes are considered potential antifungal targets. In this regard, we explored α-glucosidase as our potential target which plays a crucial role in processing mannoproteins. Previous studies have shown that inhibition of α-glucosidase leads to defects in cell wall integrity, reduced adhesion, diminished secretion of hydrolytic enzymes, alterations in immune recognition, and reduced pathogenicity. Since α-glucosidase, primarily converts carbohydrates, our study focuses on FDA-approved carbohydrate mimic drugs (Glycomimetics) with well-documented applications in various biological contexts. Through virtual screening of 114 FDA-approved carbohydrate-based drugs, a pseudo-sugar Acarbose, emerged as a top hit. Acarbose is known for its pharmacological potential in managing type 2 diabetes mellitus by targeting α-glucosidase. Our preliminary investigations indicate that Acarbose effectively inhibits C. albicans biofilm formation, reduces virulence, impairs morphological switching, and hinders the adhesion and invasion of host cells, all at very low concentrations in the nanomolar range. Furthermore, transcriptomic analysis reveals the mechanism of action of Acarbose, highlighting its role in targeting α-glucosidase.

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Mitigating Candidiasis with Acarbose by targeting Candida albicans α-Glucosidase: In- silico, In-vitro and Transcriptomic Approaches

David,

Vasudevan,

Solomon

2023

Preprint

0

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Biofilm-associated candidiasis poses a significant challenge in clinical settings due to the limited effectiveness of existing antifungal treatments. The challenges include increased pathogen virulence, multi-drug resistance, and inadequate penetration of antimicrobials into biofilm structures. One potential solution to this problem involves the development of novel drugs that can modulate fungal virulence and biofilm formation, which is essential for pathogenesis. Resistance in Candida albicans is initiated by morphological changes from yeast to hyphal form. This transition triggers a series of events such as cell wall elongation, increased adhesion, invasion of host tissues, pathogenicity, biofilm formation, and the initiation of an immune response. The cell wall is a critical interface for interactions with host cells, primarily through various cell wall proteins, particularly mannoproteins. Thus, cell wall proteins and enzymes are considered potential antifungal targets. In this regard, we explored α-glucosidase as our potential target which plays a crucial role in processing mannoproteins. Previous studies have shown that inhibition of α-glucosidase leads to defects in cell wall integrity, reduced adhesion, diminished secretion of hydrolytic enzymes, alterations in immune recognition, and reduced pathogenicity. Since α-glucosidase, primarily converts carbohydrates, our study focuses on FDA-approved carbohydrate mimic drugs (Glycomimetics) with well-documented applications in various biological contexts. Through virtual screening of 114 FDA-approved carbohydrate-based drugs, a pseudo-sugar Acarbose, emerged as a top hit. Acarbose is known for its pharmacological potential in managing type 2 diabetes mellitus by targeting α-glucosidase. Our preliminary investigations indicate that Acarbose effectively inhibits C. albicans biofilm formation, reduces virulence, impairs morphological switching, and hinders the adhesion and invasion of host cells, all at very low concentrations in the nanomolar range. Furthermore, transcriptomic analysis reveals the mechanism of action of Acarbose, highlighting its role in targeting α-glucosidase.

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Homology Modeling of Alpha-Glucosidase from Candida albicans: Sequence Analysis and Structural Validation Studies in silico

Cited by 3 publications

References 0 publications

Multi-epitopes vaccine design for surface glycoprotein against SARS-CoV-2 using immunoinformatic approach

Multi-epitopes vaccine design for surface glycoprotein against SARS-CoV-2 using immunoinformatic approach

Mitigating candidiasis with acarbose by targeting Candida albicans α-glucosidase: in-silico, in-vitro and transcriptomic approaches

Mitigating Candidiasis with Acarbose by targeting Candida albicans α-Glucosidase: In- silico, In-vitro and Transcriptomic Approaches

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