In silico investigation of the viroporin E as a vaccine target against SARS-CoV-2

Abstract

Viroporins, integral viral membrane ion channel proteins, interact with host-cell proteins deregulating physiological processes and activating inflammasomes. Severity of COVID-19 might be associated with hyperinflammation, thus we aimed at the complete immunoinformatic analysis of the SARS-CoV-2 viroporin E, P0DTC4. We also identified the human proteins interacting with P0DTC4 and the enriched molecular functions of the corresponding genes. The complete sequence of P0DTC4 in FASTA format was processed in 10 databases relative to secondary and tertiary protein structure analyses and prediction of optimal vaccine epitopes. Three more databases were accessed for the retrieval and the molecular functional characterization of the P0DTC4 human interactors. The immunoinformatics analysis resulted in the identification of 4 discontinuous B-cell epitopes along with 1 linear B-cell epitope and 11 T-cell epitopes which were found to be antigenic, immunogenic, nonallergen, nontoxin, and unable to induce autoimmunity thus fulfilling prerequisites for vaccine design. The functional enrichment analysis showed that the predicted host interactors of P0DTC4 target the cellular acetylation network. Two of the identified host-cell proteins - BRD2 and BRD4 - have been shown to be promising targets for antiviral therapy. Thus, our findings have implications for COVID-19 therapy and indicate that viroporin E could serve as a promising vaccine target against SARS-CoV-2. Validation experiments are required to complement these in silico results.

Keywords: SARS-CoV-2; acetylation; functional enrichment analysis; immunoinformatics; viroporin.

Figure 1.

Workflow of the in silico study. The SARS-CoV-2 E protein sequence in FASTA format was obtained from the Uniprot database. Thirteen computational prediction tools were used for the immunoinformatics and functional enrichment analyses.

Figure 2.

The secondary structure of the SARS-CoV-2 E viroporin as predicted by the PSIPRED 4.0 database.

Figure 3.

The three-dimensional (3-D) model of the SARS-CoV-2 E viroporin as retrieved by the PHYRE2 server. The model was built on the PDB template c5×29B (NMR structure of the SARS-CoV e protein pentameric ion channel). NMR, nuclear magnetic resonance.

Figure 4.

The B-cell linear and discontinuous epitopes that were predicted by the ElliPro tool of the immune epitope database analysis resource (IEDB) based on the predicted three-dimensional (3-D) model of the SARS-CoV-2 viroporin E.

Figure 5.

The human proteins interacting with the SARS-CoV-2 E viroporin as retrieved by the BioGRID database.

Figure 6.

The results of the g:Profiler FEA analysis with respect to the molecular function of the human genes encoding the host proteins interacting with the SARS-CoV-2 E viroporin. FEA, functional enrichment analysis.