Reverse vaccinology assisted design of a novel multi-epitope vaccine to target Wuchereria bancrofti cystatin: An immunoinformatics approach

Das, Nabarun Chandra; Gupta, Parth Sarthi Sen; Panda, Saroj Kumar; Rana, Malay Kumar; Mukherjee, Subhrajit

doi:10.1016/j.intimp.2022.109639

Cited by 15 publications

(18 citation statements)

References 85 publications

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“…The complete sequence of the F. nucleatum Fap2 protein (3799 amino acids) was retrieved in FASTA format from the National Centre for Biotechnological Information (NCBI) ( , accessed on 14 January 2023) protein database (accession number: WP016361450.1) and was used for the study. The FBCPred ( , accessed on 14 January 2023) and ABCPred ( , accessed on 14 January 2023) servers were explored to determine the B-cell epitopes present in the Fap2 protein and were further used to screen the common epitopes [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

“…3A79_C). Secondary structures of all the vaccine candidates were determined using the two feed-forward neural network methods provided in the PSIPRED 4.0 server ( , accessed on 14 January 2023), and all the structures were refined following earlier reports [ 22 , 29 ].…”

Section: Methodsmentioning

confidence: 99%

“…The binding affinity of each vaccine construct toward the different TLRs was studied using molecular docking analysis. The 3D structures of different TLRs, viz., TLR1/TLR2, TLR4–MD2 complex, and TLR5 were retrieved from RCSB protein databank ( , accessed on 14 January 2023) while TLR6 was modelled following our previous reports [ 22 , 29 , 35 ]. All the structures were refined and validated before performing the molecular docking.…”

Section: Methodsmentioning

confidence: 99%

“…In addition to NMA, molecular dynamics (MD) simulation trajectory analysis was performed using GROMACSv5.1 package (GROningenMAchine for Chemical Simulations) to cross-verify the structural stability of the vaccine–TLR complexes [ 22 , 35 ]. To construct the configuration of the docked complexes, the pdb2gmx module and force field gromos96 53a6 were used [ 22 , 35 ]. The system was then placed in a cubical box and solvated using a simple point charge (SPC) water model that exploited the editconf and solvate modules.…”

Section: Methodsmentioning

confidence: 99%

“…Finally, MD prediction was accomplished using timesteps of 10 ns for a total span of 100 ns. Grace 5.1.23 was used to plot the simulation data in different graphs, such as the root–mean–square fluctuation (RMSF), root–mean–square deviation (RMSD), a radius of gyration (Rg), and solvent accessible surface area (SASA) [ 22 , 35 ]. The conformational changes within each vaccine–TLR complex throughout the MDS process were determined by superimposing the simulated docked structures obtained from the different phases of the simulation study.…”

Section: Methodsmentioning

confidence: 99%

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Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach

et al. 2023

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Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-related deaths worldwide. The changes in gut homeostasis and microbial dysbiosis lead to the initiation of the tumorigenesis process. Several pathogenic gram-negative bacteria including Fusobacterium nucleatum are the principal contributors to the induction and pathogenesis of CRC. Thus, inhibiting the growth and survival of these pathogens can be a useful intervention strategy. Fibroblast activation protein-2 (Fap2) is an essential membrane protein of F. nucleatum that promotes the adherence of the bacterium to the colon cells, recruitment of immune cells, and induction of tumorigenesis. The present study depicts the design of an in silico vaccine candidate comprising the B-cell and T-cell epitopes of Fap2 for improving cell-mediated and humoral immune responses against CRC. Notably, this vaccine participates in significant protein–protein interactions with human Toll-like receptors, especially with TLR6 reveals, which is most likely to be correlated with its efficacy in eliciting potential immune responses. The immunogenic trait of the designed vaccine was verified by immune simulation approach. The cDNA of the vaccine construct was cloned in silico within the expression vector pET30ax for protein expression. Collectively, the proposed vaccine construct may serve as a promising therapeutic in intervening F. nucleatum-induced human CRC.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach

et al. 2023

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Revisiting Luteolin Against the Mediators of Human Metastatic Colorectal Carcinoma: A Biomolecular Approach

Chakraborty,

Midde,

Chakraborty

et al. 2024

J of Cellular Biochemistry

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Metastatic colorectal carcinoma (mCRC) is one of the prevalent subtypes of human cancers and is caused by the alterations of various lifestyle and diet‐associated factors. β‐catenin, GSK‐3β, PI3K‐α, AKT1, and NF‐κB p50 are known to be the critical regulators of tumorigenesis and immunopathogenesis of mCRC. Unfortunately, current drugs have limited efficacy, side effects and can lead to chemoresistance. Therefore, searching for a nontoxic, efficacious anti‐mCRC agent is crucial and of utmost interest. The present study demonstrates the identification of a productive and nontoxic anti‐mCRC agent through a five‐targets (β‐catenin, GSK‐3β, PI3K‐α, AKT1, and p50)‐based and three‐tier (binding affinity, pharmacokinetics, and pharmacophore) screening strategy involving a series of 30 phytocompounds having a background of anti‐inflammatory/anti‐mCRC efficacy alongside 5‐fluorouracil (FU), a reference drug. Luteolin (a phyto‐flavonoid) was eventually rendered as the most potent and safe phytocompound. This inference was verified through three rounds of validation. Firstly, luteolin was found to be effective against the different mCRC cell lines (HCT‐15, HCT‐116, DLD‐1, and HT‐29) without hampering the viability of non‐tumorigenic ones (RWPE‐1). Secondly, luteolin was found to curtail the clonogenicity of CRC cells, and finally, it also disrupted the formation of colospheroids, a characteristic of metastasis. While studying the mechanistic insights, luteolin was found to inhibit β‐catenin activity (a key regulator of mCRC) through direct physical interactions, promoting its degradation by activating GSK3‐β and ceasing its activation by inactivating AKT1 and PI3K‐α. Luteolin also inhibited p50 activity, which could be useful in mitigating mCRC‐associated proinflammatory milieu. In conclusion, our study provides evidence on the efficacy of luteolin against the critical key regulators of immunopathogenesis of mCRC and recommends further studies in animal models to determine the effectiveness efficacy of this natural compound for treating mCRC in the future.

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Helminth-derived biomacromolecules as therapeutic agents for treating inflammatory and infectious diseases: What lessons do we get from recent findings?

Chakraborty

Aravindhan

Mukherjee

2023

International Journal of Biological Macromolecules

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Reverse vaccinology assisted design of a novel multi-epitope vaccine to target Wuchereria bancrofti cystatin: An immunoinformatics approach

Cited by 15 publications

References 85 publications

Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach

Cell Surface Fibroblast Activation Protein-2 (Fap2) of Fusobacterium nucleatum as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach

Revisiting Luteolin Against the Mediators of Human Metastatic Colorectal Carcinoma: A Biomolecular Approach

Helminth-derived biomacromolecules as therapeutic agents for treating inflammatory and infectious diseases: What lessons do we get from recent findings?

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