An in silico study to unveil potential drugs and vaccine chimera for HBV capsid assembly protein: combined molecular docking and dynamics simulation approach.

Publisher: Springer Country of Publication: Germany NLM ID: 9806569 Publication Model: Electronic Cited Medium: Internet ISSN: 0948-5023 (Electronic) Linking ISSN: 09485023 NLM ISO Abbreviation: J Mol Model Subsets: MEDLINE

Original Publication: Berlin : Springer, c1996-

Computational Biology*/methods ; Molecular Docking Simulation* ; Molecular Dynamics Simulation*; Antiviral Agents/*chemistry ; Capsid Proteins/*chemistry ; Hepatitis B Vaccines/*chemistry; Amino Acid Sequence ; Binding Sites ; Capsid Proteins/immunology ; Catalytic Domain ; Cluster Analysis ; Databases, Factual ; Drug Design ; Epitopes, T-Lymphocyte/chemistry ; Epitopes, T-Lymphocyte/immunology ; Hepatitis B Vaccines/immunology ; Hepatitis B virus/immunology ; Humans ; Ligands ; Protein Binding ; Structure-Activity Relationship

Humans are a major reservoir of the hepatitis B virus (HBV), therefore promising treatment and control vaccination strategies are needed to eradicate the virus. Though promising drugs and vaccines are available against HBV, still efforts are required to enrich the therapy options. Herein, the HBV assembly protein was explored to identify novel targets for future use against HBV. Computer-aided drug designing and immune-informatics techniques were employed for the identification of putative inhibitors and vaccine ensemble against HBV using capsid assembly protein. The identified drug molecule binds with high affinity to the active pocket of the protein, and several epitopes are scanned in the protein sequence. The drug molecule, besides being a good putative inhibitor, has acceptable drug-like properties. A multi-epitope vaccine is also constructed to overcome the limitations of weakly immunogenic epitopes. In contrast to the MHC II level, the set of predicted epitopes has been recognized to interact with significant numbers of HLA alleles of MHC I. Selected epitopes are extremely virulent, antigenic, nontoxic, nonallergic, have suitable affinity to bind with the prevailing DRB*0101 allele, and also spectacle 86% mediocre population coverage. A multi-epitope peptide-based vaccine chimera having 73 amino acids was designed. It emerged as substantially immunogenic, thermally stable, robust in producing cellular as well as humoral immune responses, and had competent physicochemical properties to analyze in vitro and in vivo studies. The capsid assembly protein is a in more stable nature in the presence of the drug molecule compared to the TLR3 receptor in the vaccine presence. These particulars were confirmed by exposing the docked molecules to absolute and relative binding free energy approaches of MMGBSA/PBSA. The purpose to investigate the interactions between the vaccine and a representative TLR3 immune receptor can reveal the intermolecular affinity and possible presentation mechanism of the vaccine by TLR3 to the host immune system. It was revealed that the vaccine is showing a very good affinity of binding for the TLR3 and forming a network of hydrophobic and hydrophilic interactions. Overall, the findings of this study are promising and might be useful for further experimental validations.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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Keywords: Binding free energies; Capsid assembly protein; Docking; Drug; Hepatitis B virus; Molecular dynamics simulation; Vaccine

0 (Antiviral Agents)
0 (Capsid Proteins)
0 (Epitopes, T-Lymphocyte)
0 (Hepatitis B Vaccines)
0 (Ligands)

Date Created: 20220203 Date Completed: 20220330 Latest Revision: 20220330

20240104

10.1007/s00894-022-05042-w

35112241