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. 2021 May;39(8):2857-2872.
doi: 10.1080/07391102.2020.1756411. Epub 2020 May 2.

Reverse vaccinology approach to design a novel multi-epitope vaccine candidate against COVID-19: an in silico study

Maryam Enayatkhani  1 , Mehdi Hasaniazad  1 , Sobhan Faezi  2 , Hamed Gouklani  1 , Parivash Davoodian  1 , Nahid Ahmadi  3 , Mohammad Ali Einakian  4 , Afsaneh Karmostaji  1 , Khadijeh Ahmadi  1
Affiliations

Reverse vaccinology approach to design a novel multi-epitope vaccine candidate against COVID-19: an in silico study

Maryam Enayatkhani et al. J Biomol Struct Dyn. 2021 May.

Abstract

At present, novel Coronavirus (2019-nCoV, the causative agent of COVID-19) has caused worldwide social and economic disruption. The disturbing statistics of this infection promoted us to develop an effective vaccine candidate against the COVID-19. In this study, bioinformatics approaches were employed to design and introduce a novel multi-epitope vaccine against 2019-nCoV that can potentially trigger both CD4+ and CD8+ T-cell immune responses and investigated its biological activities by computational tools. Three known antigenic proteins (Nucleocapsid, ORF3a, and Membrane protein, hereafter called NOM) from the virus were selected and analyzed for prediction of the potential immunogenic B and T-cell epitopes and then validated using bioinformatics tools. Based on in silico analysis, we have constructed a multi-epitope vaccine candidate (NOM) with five rich-epitopes domain including highly scored T and B-cell epitopes. After predicting and evaluating of the third structure of the protein candidate, the best 3 D predicted model was applied for docking studies with Toll-like receptor 4 (TLR4) and HLA-A*11:01. In the next step, molecular dynamics (MD) simulation was used to evaluate the stability of the designed fusion protein with TLR4 and HLA-A*11:01 receptors. MD studies demonstrated that the NOM-TLR4 and NOM-HLA-A*11:01 docked models were stable during simulation time. In silico evaluation showed that the designed chimeric protein could simultaneously elicit humoral and cell-mediated immune responses. Communicated by Ramaswamy H. Sarma.

Keywords: COVID-19; Coronavirus; Epitope; Immunoinformatics; Vaccine.

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Figures

Figure 1.
Figure 1.
Strategies employed in the overall study.
Figure 2.
Figure 2.
The schematic diagram of the vaccine candidate construct consists of N, ORF3a and M proteins epitopes of the COVID-19 linked together with AAA linkers.
Figure 3.
Figure 3.
(a-c) Prediction and validation of tertiary structure of the NOM recombinant protein using (a) Prediction of the tertiary structure of the NOM recombinant protein, (b) ProSA web, (c) Ramachandran plot.
Figure 4.
Figure 4.
Three-dimensional representation of discontinuous epitopes of the NOM designed protein. The epitopes are represented by a yellow surface, and the bulk of the polyprotein is represented in grey sticks.
Figure 5.
Figure 5.
The RMSD values of the simulated monomer forms of the proteins throughput the 100 ns of production runs.
Figure 6.
Figure 6.
The total energy plots of the simulations.
Figure 7.
Figure 7.
The RMSD values of each protein in the simulated complexes throughout the 100 ns of production runs.
Figure 8.
Figure 8.
The RMSF values of each protein in the simulated complexes compared to the simulated monomer forms of the proteins throughout the 100 ns of production runs. a, The comparison of the RMSF values of NOM recombinant protein in the complexes with the monomer form. b, The comparison of the RMSF values of HLA-A*11:01 in the complexes with the simulated monomer form. c, The comparison of the RMSF values of TLR4 in the complexes with the simulated monomer form.
Figure 9.
Figure 9.
The graphical illustration of the monomer forms and the complex forms of the NOM recombinant protein and the HLA-A*11:01 and TLR4 immune receptors.
See this image and copyright information in PMC

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