Rational Design of Hyper-glycosylated Human Chorionic Gonadotropin Analogs (A Bioinformatics Approach)

Nabizadeh, Zahra; Minuchehr, Zarrin; Shabani, Ali Akbar

doi:10.2174/1570180817666200225101938

Cited by 4 publications

(1 citation statement)

References 52 publications

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“…The MD simulation analysis was performed for 50 ns to compute the docked complex's stability using the GROMACS program [ 75 ] with GROMOS96 54A7 force field [ 76 ]. The MD run was performed in about two days for each selected complex, using the described conditions in our prior works [ 77 , 78 ]. Briefly, the target complexes were placed within a proper cubic box, solvated applying the TIP3P water type, and neutralized by adding sufficient Na + /Cl ions.…”

Section: Design and Construction Of Epitope-based Vaccinementioning

confidence: 99%

In silico designing of a novel epitope-based candidate vaccine against Streptococcus pneumoniae with introduction of a new domain of PepO as adjuvant

et al. 2022

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Background Streptococcus pneumoniae is the leading reason for invasive diseases including pneumonia and meningitis, and also secondary infections following viral respiratory diseases such as flu and COVID-19. Currently, serotype-dependent vaccines, which have several insufficiency and limitations, are the only way to prevent pneumococcal infections. Hence, it is plain to need an alternative effective strategy for prevention of this organism. Protein-based vaccine involving conserved pneumococcal protein antigens with different roles in virulence could provide an eligible alternative to existing vaccines. Methods In this study, PspC, PhtD and PsaA antigens from pneumococcus were taken to account to predict B-cell and helper T-cell epitopes, and epitope-rich regions were chosen to build the construct. To enhance the immunogenicity of the epitope-based vaccine, a truncated N-terminal fragment of pneumococcal endopeptidase O (PepO) was used as a potential TLR2/4 agonist which was identified by molecular docking studies. The ultimate construct was consisted of the chosen epitope-rich regions, along with the adjuvant role (truncated N-PepO) and suitable linkers. Results The epitope-based vaccine was assessed as regards physicochemical properties, allergenicity, antigenicity, and toxicity. The 3D structure of the engineered construct was modeled, refined, and validated. Molecular docking and simulation of molecular dynamics (MD) indicated the proper and stable interactions between the vaccine and TLR2/4 throughout the simulation periods. Conclusions For the first time this work presents a novel vaccine consisting of epitopes of PspC, PhtD, and PsaA antigens which is adjuvanted with a new truncated domain of PepO. The computational outcomes revealed that the suggested vaccine could be deemed an efficient therapeutic vaccine for S. pneumoniae; nevertheless, in vitro and in vivo examinations should be performed to prove the potency of the candidate vaccine.

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Section: Design and Construction Of Epitope-based Vaccinementioning

confidence: 99%

In silico designing of a novel epitope-based candidate vaccine against Streptococcus pneumoniae with introduction of a new domain of PepO as adjuvant

et al. 2022

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Design, development, and assessment of a novel multi-peptide vaccine targeting PspC, PsaA, and PhtD proteins of Streptococcus pneumoniae

Bahadori,

Shafaghi,

Sabzevari

et al. 2024

International Journal of Biological Macromolecules

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Immunoinformatics-aided design of a new multi-epitope vaccine adjuvanted with domain 4 of pneumolysin against Streptococcus pneumoniae strains

et al. 2023

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Background Streptococcus pneumoniae (Pneumococcus) has remained a leading cause of fatal infections such as pneumonia, meningitis, and sepsis. Moreover, this pathogen plays a major role in bacterial co-infection in patients with life-threatening respiratory virus diseases such as influenza and COVID-19. High morbidity and mortality in over one million cases, especially in very young children and the elderly, are the main motivations for pneumococcal vaccine development. Due to the limitations of the currently marketed polysaccharide-based vaccines, non-serotype-specific protein-based vaccines have received wide research interest in recent years. One step further is to identify high antigenic regions within multiple highly-conserved proteins in order to develop peptide vaccines that can affect various stages of pneumococcal infection, providing broader serotype coverage and more effective protection. In this study, immunoinformatics tools were used to design an effective multi-epitope vaccine in order to elicit neutralizing antibodies against multiple strains of pneumococcus. Results The B- and T-cell epitopes from highly protective antigens PspA (clades 1–5) and PhtD were predicted and immunodominant peptides were linked to each other with proper linkers. The domain 4 of Ply, as a potential TLR4 agonist adjuvant candidate, was attached to the end of the construct to enhance the immunogenicity of the epitope vaccine. The evaluation of the physicochemical and immunological properties showed that the final construct was stable, soluble, antigenic, and non-allergenic. Furthermore, the protein was found to be acidic and hydrophilic in nature. The protein 3D-structure was built and refined, and the Ramachandran plot, ProSA–web, ERRAT, and Verify3D validated the quality of the final model. Molecular docking analysis showed that the designed construct via Ply domain 4 had a strong interaction with TLR4. The structural stability of the docked complex was confirmed by molecular dynamics. Finally, codon optimization was performed for gene expression in E. coli, followed by in silico cloning in the pET28a(+) vector. Conclusion The computational analysis of the construct showed acceptable results, however, the suggested vaccine needs to be experimentally verified in laboratory to ensure its safety and immunogenicity.

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Rational Design of Hyper-glycosylated Human Chorionic Gonadotropin Analogs (A Bioinformatics Approach)

Cited by 4 publications

References 52 publications

In silico designing of a novel epitope-based candidate vaccine against Streptococcus pneumoniae with introduction of a new domain of PepO as adjuvant

In silico designing of a novel epitope-based candidate vaccine against Streptococcus pneumoniae with introduction of a new domain of PepO as adjuvant

Design, development, and assessment of a novel multi-peptide vaccine targeting PspC, PsaA, and PhtD proteins of Streptococcus pneumoniae

Immunoinformatics-aided design of a new multi-epitope vaccine adjuvanted with domain 4 of pneumolysin against Streptococcus pneumoniae strains

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