Exploring SARS-COV-2 structural proteins to design a multi-epitope vaccine using immunoinformatics approach: An in silico study

In December 2019, a new virus called SARS-CoV-2 was reported in China and quickly spread to other parts of the world. The development of SARS-COV-2 vaccines has recently received much attention from numerous researchers. The present study aims to design an effective multi-epitope vaccine against SARS-COV-2 using the reverse vaccinology method. In this regard, structural proteins from SARS-COV-2, including the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, were selected as target antigens for epitope prediction. A total of five helper T lymphocytes (HTL) and five cytotoxic T lymphocytes (CTL) epitopes were selected after screening the predicted epitopes for antigenicity, allergenicity, and toxicity. Subsequently, the selected HTL and CTL epitopes were fused via flexible linkers. Next, the cholera toxin B-subunit (CTxB) as an adjuvant was linked to the N-terminal of the chimeric structure. The proposed vaccine was analyzed for the properties of physicochemical, antigenicity, and allergenicity. The 3D model of the vaccine construct was predicted and docked with the Toll-like receptor 4 (TLR4). The molecular dynamics (MD) simulation was performed to evaluate the stable interactions between the vaccine construct and TLR4. The immune simulation was also conducted to explore the immune responses induced by the vaccine. Finally, in silico cloning of the vaccine construct into the pET-28 (+) vector was conducted. The results obtained from all bioinformatics analysis stages were satisfactory; however, in vitro and in vivo tests are essential to validate these results.

• Publication year

  2021

• Venue

  Comput. Biol. Medicine

• Publication date

  2021-04-20

• Fields of study

  Medicine, Computer Science

• Identifiers
  DOI 10.1016/j.compbiomed.2021.104390PMID 33895459PMCID 8055380
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The novel coronavirus outbreak in Wuhan, China

  2020cited by this paper
• Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

  2020cited by this paper
• An in silico deep learning approach to multi-epitope vaccine design: a SARS-CoV-2 case study

  2020cited by this paper
• Lead SARS-CoV-2 Candidate Vaccines: Expectations from Phase III Trials and Recommendations Post-Vaccine Approval

  2020cited by this paper
• Structure and dynamics of membrane protein in SARS-CoV-2

  2020cited by this paper
• In-silico identification of new inhibitors for Low-density lipoprotein receptor-related protein6 (LRP6)

  2020cited by this paper
• Multiepitope Subunit Vaccine Design against COVID-19 Based on the Spike Protein of SARS-CoV-2: An In Silico Analysis

  2020cited by this paper
• Scrutinizing the SARS-CoV-2 protein information for designing an effective vaccine encompassing both the T-cell and B-cell epitopes

  2020cited by this paper
• Design and optimization of a subunit vaccine targeting COVID-19 molecular shreds using an immunoinformatics framework

  2020cited by this paper
• Design of novel multiepitope constructs-based peptide vaccine against the structural S, N and M proteins of human COVID-19 using immunoinformatics analysis

  2020cited by this paper
• Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches

  2020cited by this paper
• Secondary structure of the SARS-CoV-2 5’-UTR

  2020cited by this paper
• Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2

  2020influential reference
• Genomic Cues From Beta-Coronaviruses and Mammalian Hosts Sheds Light on Probable Origins and Infectivity of SARS-CoV-2 Causing COVID-19

  2020cited by this paper
• Comparing the binding properties of peptides mimicking the Envelope protein of SARS‐CoV and SARS‐CoV‐2 to the PDZ domain of the tight junction‐associated PALS1 protein

  2020cited by this paper
• Anti-COVID-19 multi-epitope vaccine designs employing global viral genome sequences

  2020cited by this paper
• Exploring the SARS-CoV-2 structural proteins for multi-epitope vaccine development: an in-silico approach

  2020cited by this paper
• Wild birds as reservoirs for diverse and abundant gamma- and deltacoronaviruses

  2020cited by this paper
• Genomic mutations and changes in protein secondary structure and solvent accessibility of SARS-CoV-2 (COVID-19 virus)

  2020cited by this paper
• The Global and Local Distribution of RNA Structure throughout the SARS-CoV-2 Genome

  2020influential reference
• Excavating SARS‐coronavirus 2 genome for epitope‐based subunit vaccine synthesis using immunoinformatics approach

  2020cited by this paper
• A candidate multi-epitope vaccine against SARS-CoV-2

  2020cited by this paper
• A proposed role for the SARS‐CoV‐2 nucleocapsid protein in the formation and regulation of biomolecular condensates

  2020cited by this paper
• In silico multi-epitope vaccine against covid19 showing effective interaction with HLA-B*15:03

  2020cited by this paper
• Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2

  2020cited by this paper
• The COVID-19 pandemic.

  2020cited by this paper
• Designing a multi-epitope peptide based vaccine against SARS-CoV-2

  2020cited by this paper
• Reverse vaccinology approach to design a novel multi-epitope vaccine candidate against COVID-19: an in silico study

  2020cited by this paper
• Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis

  2020cited by this paper
• The Architecture of SARS-CoV-2 Transcriptome

  2020cited by this paper
• SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

  2020cited by this paper
• Consistent Detection of 2019 Novel Coronavirus in Saliva

  2020cited by this paper
• Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China

  2020cited by this paper
• 2019-nCoV transmission through the ocular surface must not be ignored

  2020cited by this paper
• Updates on Wuhan 2019 novel coronavirus epidemic

  2020cited by this paper
• Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

  2020cited by this paper
• Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies

  2020cited by this paper
• Emerging viruses and current strategies for vaccine intervention

  2019cited by this paper
• Development of multi-epitope driven subunit vaccine against Fasciola gigantica using immunoinformatics approach.

  2019cited by this paper
• Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development

  2019cited by this paper
• Immunoinformatics Design of a Novel Multi-Epitope Peptide Vaccine to Combat Multi-Drug Resistant Infections caused by Vibrio vulnificus.

  2019cited by this paper
• Epitope‐based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: an immune-informatics study

  2019cited by this paper
• Cytokines and Chemokines

  2018cited by this paper
• Improved methods for predicting peptide binding affinity to MHC class II molecules

  2018influential reference
• Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice

  2017cited by this paper
• New additions to the ClusPro server motivated by CAPRI

  2017cited by this paper
• Development of a multi-epitope peptide vaccine inducing robust T cell responses against brucellosis using immunoinformatics based approaches.

  2017cited by this paper
• Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection

  2017influential reference
• Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

  2017cited by this paper
• The ClusPro web server for protein–protein docking

  2017influential reference
• T-Cell Epitope Prediction.

  2017cited by this paper
• Computer-aided designing of immunosuppressive peptides based on IL-10 inducing potential

  2017cited by this paper
• Exploring Leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach

  2017cited by this paper
• Computer aided epitope design as a peptide vaccine component against Lassa virus

  2017cited by this paper
• Synonymous codon usage pattern in glycoprotein gene of rabies virus.

  2016influential reference
• Advances in Antiviral Therapies Targeting Toll-like Receptors

  2016cited by this paper
• 3Drefine: an interactive web server for efficient protein structure refinement

  2016cited by this paper
• GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers

  2015cited by this paper
• Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition

  2015cited by this paper
• Tackling Exascale Software Challenges in Molecular Dynamics Simulations with GROMACS

  2015cited by this paper
• The I-TASSER Suite: protein structure and function prediction

  2014cited by this paper
• Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds

  2013influential reference
• 3Drefine: Consistent protein structure refinement by optimizing hydrogen bonding network and atomic‐level energy minimization

  2013cited by this paper
• How good is automated protein docking?

  2013influential reference
• Prediction of IL4 Inducing Peptides

  2013cited by this paper
• Designing of interferon-gamma inducing MHC class-II binders

  2013cited by this paper
• i3Drefine Software for Protein 3D Structure Refinement and Its Assessment in CASP10

  2013cited by this paper
• GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit

  2013cited by this paper
• In Silico Approach for Predicting Toxicity of Peptides and Proteins

  2013cited by this paper
• Study designs for the nonclinical safety testing of new vaccine products.

  2012cited by this paper
• CD4+T Cells: Differentiation and Functions

  2012cited by this paper
• License to kill: Formulation requirements for optimal priming of CD8(+) CTL responses with particulate vaccine delivery systems.

  2012cited by this paper
• SARS-CoV Regulates Immune Function-Related Gene Expression in Human Monocytic Cells

  2012cited by this paper
• Fusion of CtxB with StxB, Cloning and Expression of in Esherichia coli: A challenge for Improvement of Immune Response Against StxB

  2011cited by this paper
• Recent trends in vaccine delivery systems: A review

  2011cited by this paper
• Computer aided selection of candidate vaccine antigens

  2010cited by this paper
• I-TASSER: a unified platform for automated protein structure and function prediction

  2010cited by this paper
• Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System

  2010cited by this paper
• High-throughput prediction of protein antigenicity using protein microarray data

  2010cited by this paper
• Predicting linear B‐cell epitopes using string kernels

  2008influential reference
• ElliPro: a new structure-based tool for the prediction of antibody epitopes

  2008cited by this paper
• Bioinformatic Approach for Identifying Parasite and Fungal Candidate Subunit Vaccines

  2008cited by this paper
• I-TASSER server for protein 3D structure prediction

  2008cited by this paper
• Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction

  2007influential reference
• Identifying candidate subunit vaccines using an alignment-independent method based on principal amino acid properties.

  2007cited by this paper
• Prediction of linear B-cell epitopes using amino acid pair antigenicity scale

  2007influential reference
• Strategy for selecting and characterizing linker peptides for CBM9‐tagged fusion proteins expressed in Escherichia coli

  2007cited by this paper
• Intranasal vaccination with peptides and cholera toxin subunit B as Adjuvant to enhance mucosal and systemic immunity to respiratory syncytial virus

  2007cited by this paper
• JCat: a novel tool to adapt codon usage of a target gene to its potential expression host

  2005cited by this paper
• Old and new vaccine approaches.

  2003cited by this paper
• IFNs and STATs in innate immunity to microorganisms.

  2002cited by this paper
• Reverse vaccinology.

  2000cited by this paper
• Protein identification and analysis tools in the ExPASy server.

  1999cited by this paper
• A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen

  1997cited by this paper
• AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR

  1996cited by this paper
• GOR method for predicting protein secondary structure from amino acid sequence.

  1996influential reference
• Thirty years of environmental health research--and growing.

  1996cited by this paper
• LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions.

  1995cited by this paper
• DNA and peptide sequences and chemical processes multivariately modelled by principal component analysis and partial least-squares projections to latent structures

  1993cited by this paper
• Recognition of errors in three‐dimensional structures of proteins

  1993cited by this paper

• Immunoinformatics-Based development of a Multi-Epitope vaccine candidate targeting coinfection by Klebsiella pneumoniae and Acinetobacter baumannii

  2025cites this paper
• Rational in-silico design of a multi-epitope vaccine against human Rhinovirus an immune simulation and molecular dynamics simulation approach

  2025cites this paper
• Development of a multi-epitope vaccine candidate to combat SARS-CoV-2 and dengue virus co-infection through an immunoinformatic approach

  2025cites this paper
• Synthetic Epoxy–Phenanthridine–Triazole Conjugates Induce Dual Redox Imbalance and Metabolic Remodeling in Breast Cancer Cells: An Integrative Mechanistic Evaluation from Synthesis to Mitochondrial Collapse

  2025cites this paper
• Using immunoinformatics and bioinformatics approach to design novel and effective rational in-silico vaccine against human Astrovirus targeting the capsid polyprotein VP90: a silent threat to global gastrointestinal tract

  2025cites this paper
• Immunoinformatics design of multi-epitope vaccine candidates against "ESKAPE" pathogens as nosocomial infection

  2025cites this paper
• Study on immunogenicity of recombinant ferritin hemagglutinin of canine distemper virus

  2025cites this paper
• Molecular dynamics simulation shows enhanced stability in scaffold-based macromolecule, designed by protein engineering: a novel methodology adapted for converting Mtb Ag85A to a multi-epitope vaccine

  2025cites this paper
• Reverse Vaccinology Approach to Identify Novel and Immunogenic Targets against Streptococcus gordonii

  2024cites this paper
• Designing a multi-epitope influenza vaccine: an immunoinformatics approach

  2024cites this paper
• Challenges and considerations in multi-epitope vaccine design surrounding toll-like receptors.

  2024cites this paper
• Immunized mice naturally process in silico-derived peptides from the nucleocapsid of SARS-CoV-2

  2023cites this paper
• Developing a multiepitope vaccine for the prevention of SARS-CoV-2 and monkeypox virus co-infection: A reverse vaccinology analysis

  2023cites this paper
• In silico design and immunoinformatics analysis of a universal multi-epitope vaccine against monkeypox virus

  2023cites this paper
• Molecular Mimicry Mapping in Streptococcus pneumoniae: Cues for Autoimmune Disorders and Implications for Immune Defense Activation

  2023cites this paper
• Coevolution based immunoinformatics approach considering variability of epitopes to combat different strains: A case study using spike protein of SARS-CoV-2

  2023cites this paper
• A First Computational Frame for Recognizing Heparin-Binding Protein

  2023cites this paper
• Interaction of SARS-CoV-2 with host cells and antibodies: experiment and simulation.

  2023cites this paper
• Development of a tetravalent subunit vaccine against dengue virus through a vaccinomics approach

  2023cites this paper
• Reverse vaccinology-based prediction of a multi-epitope SARS-CoV-2 vaccine and its tailoring to new coronavirus variants

  2022cites this paper
• Mapping Potential Vaccine Candidates Predicted by VaxiJen for Different Viral Pathogens between 2017–2021—A Scoping Review

  2022cites this paper
• Looking for SARS-CoV-2 therapeutics through computational approaches.

  2022cites this paper
• Daphnoretin from Carthamus tinctorius as a Potential Inflammatory Inhibitor in COVID-19 by Binding to Toll-like Receptor-4: An in silico Molecular Docking Study

  2022cites this paper
• gp120 Alters Its Conformation to Enhance Evasiveness and Infectivity

  2021cites this paper
• IDbSV: An Open-Access Repository for Monitoring SARS-CoV-2 Variations and Evolution

  2021influential citation
• Role of artificial intelligence in peptide vaccine design against RNA viruses

  2021cites this paper