Exploiting reverse vaccinology approach for the design of a multiepitope subunit vaccine against the major SARS-CoV-2 variants

Campos, Daniel Melo de Oliveira; Silva, Maria Karolaynne da; Barbosa, Emmanuel Duarte; Leow, Chiuan Yee; Fulco, U. L.

doi:10.1016/j.compbiolchem.2022.107754

Cited by 13 publications

(17 citation statements)

References 127 publications

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“…This approach combines quantum mechanics for the ligand-receptor interactions with molecular mechanics for the surrounding environment, allowing for a more accurate representation of the system's behavior. QM/MM methods have solidified their position as advanced computational tools for studying biomolecular systems, as evidenced by the increasing number of publications utilizing these methods 20 , 26 , 53 , 54 . this procedure consists of taking an input sequence in FASTA format and implementing three techniques: single and multiple template threading, along with prediction of alignment quality 7 .…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, in silico gene cloning was conducted using the pET-28a( +) vector. This is a consolidated approach that has been used in several studies with pathogenic microorganisms such as SARS-CoV-2 20 , Streptococcus pneumoniae 21 , and Alkhurma hemorrhagic fever virus 22 as well as with other arboviruses such as dengue 23 , chikungunya 24 , and Mayaro virus 25 , 26 .…”

Section: Introductionmentioning

confidence: 99%

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Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development

da Silva,

Rodrigues-Neto

et al. 2024

Sci Rep

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Yellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ($$\beta$$ β -defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development

da Silva,

Rodrigues-Neto

et al. 2024

Sci Rep

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“…This choice ensures the accuracy and reliability of our calculations, as the 6-311 + G (d, p) basis set has been proven to predict the electronic structure, binding interactions with biological receptors, and spectroscopic and thermodynamic properties of a variety of organic molecules. 19,[43][44][45][46] In addition, a dielectric constant was included through the conductor-like polarizable continuum model (CPCM) to mimic the influence of the electrostatic environment of the drug and improve the calculations. 19,47 The following values were calculated to electronically characterize the compounds: total energy (the total energy of the molecule), binding energy (the interaction energy between all the atoms in the molecule, also known as cohesive energy), highest occupied molecular orbital (HOMO) energy (the energy of the highest occupied molecular orbital), lowest unoccupied molecular orbital (LUMO) (the energy of the lowest unoccupied molecular orbital), band gap and electrophilicity index (ω) were meticulously examined.…”

Section: Quantum Energies and Quantum Chemical Descriptors Using Mole...mentioning

confidence: 99%

A robust computational quest: Discovering potential hits to improve the treatment of pyrazinamide‐resistant Mycobacterium tuberculosis

Shahab,

de Farias Morais,

Akash

et al. 2024

J Cellular Molecular Medi

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The rise of pyrazinamide (PZA)‐resistant strains of Mycobacterium tuberculosis (MTB) poses a major challenge to conventional tuberculosis (TB) treatments. PZA, a cornerstone of TB therapy, must be activated by the mycobacterial enzyme pyrazinamidase (PZase) to convert its active form, pyrazinoic acid, which targets the ribosomal protein S1. Resistance, often associated with mutations in the RpsA protein, complicates treatment and highlights a critical gap in the understanding of structural dynamics and mechanisms of resistance, particularly in the context of the G97D mutation. This study utilizes a novel integration of computational techniques, including multiscale biomolecular and molecular dynamics simulations, physicochemical and medicinal chemistry predictions, quantum computations and virtual screening from the ZINC and Chembridge databases, to elucidate the resistance mechanism and identify lead compounds that have the potential to improve treatment outcomes for PZA‐resistant MTB, namely ZINC15913786, ZINC20735155, Chem10269711, Chem10279789 and Chem10295790. These computational methods offer a cost‐effective, rapid alternative to traditional drug trials by bypassing the need for organic subjects while providing highly accurate insight into the binding sites and efficacy of new drug candidates. The need for rapid and appropriate drug development emphasizes the need for robust computational analysis to justify further validation through in vitro and in vivo experiments.

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“…The allergenicity, toxicity, and solubility of peptides were assessed via bioinformatics tools to verify the validity and potency of the construct. Campos et al [ 30 ] identified the 7 mutations with strong binding affinity, high antigenicity, allergenicity, immunogenicity, and nontoxicity present in spike protein of all SARS-CoV-2 variants that we could readily use in the construction of prototype peptide vaccine. A novel multi-epitopes peptide vaccine construct against the Jaagsiekte retrovirus, Mahmoud et al [ 31 ] predicted that these peptide vaccines include antigenicity, sensitization, toxicity, and stability.…”

Section: Introductionmentioning

confidence: 99%

Bionics design of affinity peptide inhibitors for SARS-CoV-2 RBD to block SARS-CoV-2 RBD-ACE2 interactions

Liu

Jiang

et al. 2023

Heliyon

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Exploiting reverse vaccinology approach for the design of a multiepitope subunit vaccine against the major SARS-CoV-2 variants

Cited by 13 publications

References 127 publications

Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development

Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development

A robust computational quest: Discovering potential hits to improve the treatment of pyrazinamide‐resistant Mycobacterium tuberculosis

Bionics design of affinity peptide inhibitors for SARS-CoV-2 RBD to block SARS-CoV-2 RBD-ACE2 interactions

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