Immunoinformatics and Molecular Docking Studies Predicted Potential Multiepitope-Based Peptide Vaccine and Novel Compounds against Novel SARS-CoV-2 through Virtual Screening

Abstract

Background: Coronaviruses (CoVs) are enveloped positive-strand RNA viruses which have club-like spikes at the surface with a unique replication process. Coronaviruses are categorized as major pathogenic viruses causing a variety of diseases in birds and mammals including humans (lethal respiratory dysfunctions). Nowadays, a new strain of coronaviruses is identified and named as SARS-CoV-2. Multiple cases of SARS-CoV-2 attacks are being reported all over the world. SARS-CoV-2 showed high death rate; however, no specific treatment is available against SARS-CoV-2.

Methods: In the current study, immunoinformatics approaches were employed to predict the antigenic epitopes against SARS-CoV-2 for the development of the coronavirus vaccine. Cytotoxic T-lymphocyte and B-cell epitopes were predicted for SARS-CoV-2 coronavirus protein. Multiple sequence alignment of three genomes (SARS-CoV, MERS-CoV, and SARS-CoV-2) was used to conserved binding domain analysis.

Results: The docking complexes of 4 CTL epitopes with antigenic sites were analyzed followed by binding affinity and binding interaction analyses of top-ranked predicted peptides with MHC-I HLA molecule. The molecular docking (Food and Drug Regulatory Authority library) was performed, and four compounds exhibiting least binding energy were identified. The designed epitopes lead to the molecular docking against MHC-I, and interactional analyses of the selected docked complexes were investigated. In conclusion, four CTL epitopes (GTDLEGNFY, TVNVLAWLY, GSVGFNIDY, and QTFSVLACY) and four FDA-scrutinized compounds exhibited potential targets as peptide vaccines and potential biomolecules against deadly SARS-CoV-2, respectively. A multiepitope vaccine was also designed from different epitopes of coronavirus proteins joined by linkers and led by an adjuvant.

Conclusion: Our investigations predicted epitopes and the reported molecules that may have the potential to inhibit the SARS-CoV-2 virus. These findings can be a step towards the development of a peptide-based vaccine or natural compound drug target against SARS-CoV-2.

Figure 1

The organization of Coronavirus genome, which contains a 5′ end, a leader sequence, replicase protein (important for replication of whole genome), spikes, envelope, membrane, nucleocapsid, and a 3′UTR poly-A-tail end.

Figure 2

Surface accessibility, surface flexibility, Parker's hydrophilicity, and antigenicity predictions evaluated by the IEDB server for nonstructural protein (PDB: 6LU7) representing the surface probability scores of the residues (a–d), respectively. Sequence positions are represented along the x-axis while probability scores are represented along the y-axis.

Figure 3

Peptide-MHC class I HLA-B binding interacting residues of four top-ranked peptides represented in different colors.

Figure 4

Four selected FDA-approved drugs (a) FDA-7, (b) FDA378, (c) FDA670, and (d) FDA592.

Figure 5

Nonstructural protein (PDB: 6LU7) has three domains, domain I from 8-99a.a (green), domain II from 100-183a.a (cyan), and domain III from 200-306a.a (brown). A conserved binding pocket present in domain II is observed while docked with FDA ligands. Top 4 ligands from FDA library have conserved interacting residues, FDA-7 (olive green), FDA-378 (skin), FDA-592 (purple), and FDA-670 (blue).

Figure 6

A multiepitope vaccine construct led by an adjuvant and all epitopes joined with linkers.

Figure 7

Sequence (a) elaborating the linkers (AAY, GPGPG, and EAAAK with purple, blue, and red color, respectively) Brown color adjuvant is also mentioned. MEV 3D structure is displayed (b); purple color indicates beta-sheets cyan color for loops, and the rest of blue color indicates turns in MEV. The Ramachandran plot evaluation of MEV is also elaborated (c).

Figure 8

All interacting residues from MEV are shown in green color, and the rest of all red residues are TLR3-interacting residues.

Figure 9

All interacting residues from MEV shown in green color and residues of TLR8 interacting residues in red color.