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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. [ABSTRACT FROM AUTHOR]

As SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to inflict chaos globally, a new variant officially known as B.1.1.529 was reported in South Africa and was found to harbor 30 mutations in the spike protein. It is too early to speculate on transmission and hospitalizations. Hence, more analyses are required, particularly to connect the genomic patterns to the phenotypic attributes to reveal the binding differences and antibody response for this variant, which can then be used for therapeutic interventions. Given the urgency of the required analysis and data on the B.1.1.529 variant, we have performed a detailed investigation to provide an understanding of the impact of these novel mutations on the structure, function, and binding of RBD to hACE2 and mAb to the NTD of the spike protein. The differences in the binding pattern between the wild type and B.1.1.529 variant complexes revealed that the key substitutions Asn417, Ser446, Arg493, and Arg498 in the B.1.1.529 RBD caused additional interactions with hACE2 and the loss of key residues in the B.1.1.529 NTD resulted in decreased interactions with three CDR regions (1–3) in the mAb. Further investigation revealed that B.1.1.529 displayed a stable dynamic that follows a global stability trend. In addition, the dissociation constant (K D), hydrogen bonding analysis, and binding free energy calculations further validated the findings. Hydrogen bonding analysis demonstrated that significant hydrogen bonding reprogramming took place, which revealed key differences in the binding. The total binding free energy using MM/GBSA and MM/PBSA further validated the docking results and demonstrated significant variations in the binding. This study is the first to provide a basis for the higher infectivity of the new SARS-CoV-2 variants and provides a strong impetus for the development of novel drugs against them. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is the world's most prevalent chronic viral infection. More than 350 million individuals are chronic carriers of the virus, with an estimated 2 billion infected persons. For instance, the role of HBx protein in attachment and infection is very obvious and consequently deemed as an important druggable target. Targeting the interface and discovering novel drugs greatly advanced the field of therapeutics development. Therefore, in the current study, HBx to Bcl-xL is abrogated on high-affinity carbon nanotubes using computational structural biology tools. Our analysis revealed that among the total 62 carbon fullerenes, only 13 compounds exhibited inhibitory activity against HBx, which was further confirmed through IFD-based rescoring. Structural dynamics investigation revealed stable binding, compactness, and hydrogen bonds reprogramming. Moreover, the binding free energy calculation results revealed that the top hits1-4 possess the total binding energy of −54.36 kcal/mol (hit1), −50.81 kcal/mol (hit2), −47.09 kcal/mol (hit3), and −45.59 kcal/mol for hit4. In addition, the predicted KD values and bioactivity scores further validated the inhibitory potential of these top hits. The identified compounds need further in vitro and in vivo validation to aid the treatment process of HBV. [ABSTRACT FROM AUTHOR]