Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus 2 (SARS-COV-2) is a significant threat to global health security. Till date, no completely effective drug or vaccine is available to cure COVID-19. Therefore, an effective vaccine against SARS-COV-2 is crucially needed. This study was conducted to design an effective multiepitope based vaccine (MEV) against SARS-COV-2. Seven highly antigenic proteins of SARS-COV-2 were selected as targets and different epitopes (B-cell and T-cell) were predicted. Highly antigenic and overlapping epitopes were shortlisted. Selected epitopes indicated significant interactions with the HLA-binding alleles and 99.93% coverage of the world's population. Hence, 505 amino acids long MEV was designed by connecting 16 MHC class I and eleven MHC class II epitopes with suitable linkers and adjuvant. MEV construct was non-allergenic, antigenic, stable and flexible. Furthermore, molecular docking followed by molecular dynamics (MD) simulation analyses, demonstrated a stable and strong binding affinity of MEV with human pathogenic toll-like receptors (TLR), TLR3 and TLR8. Finally, MEV codons were optimized for its in silico cloning into Escherichia coli K-12 system, to ensure its increased expression. Designed MEV in present study could be a potential candidate for further vaccine production process against COVID-19. However, to ensure its safety and immunogenic profile, the proposed MEV needs to be experimentally validated.

Discovery of selective inhibitors for cyclic AMP response element-binding protein: a combined ligand and structure-based resources pipeline.

Bromodomains are epigenetic readers of acetyl-lysine involved in chromatin remodeling and transcriptional regulations. Over the past few years, extensive research has been carried out to discover small-molecule inhibitors against bromodomains to treat various diseases. Cyclic AMP response element-binding protein (CREBBP) bromodomain has emerged as a hot target for cancer therapy. This study aims at discovering new inhibitors against CREBBP bromodomain using ligand-based molecular docking. A library of 2168 lead-like compounds were docked into the Kac binding site of CREBBP bromodomain. On the basis of the energy score and interaction analysis, six compounds were selected. In order to validate the stability of these six protein-ligand complexes 20 ns molecular dynamics simulations and principal component analyses were carried out. Based on the different analyses these six compounds may provide valuable information for developing CREBBP selective inhibitors.

In-silico identification and evaluation of plant flavonoids as dengue NS2B/NS3 protease inhibitors using molecular docking and simulation approach.

Dengue infection is prevailing among the people not only from the developing countries but also from the developed countries due to its high morbidity rate around the globe. Hence, due to the unavailability of any suitable vaccine for rigorous dengue virus (DENV), the only mode of its treatment is prevention. The circumstances require an urgent development of efficient and practical treatment to deal with these serotypes. The severe effects and cost of synthetic vaccines simulated researchers to find anti-viral agents from medicinal plants. Flavonoids present in medicinal plants, holds anti-viral activity and can be used as vaccine against viruses. Therefore, present study was planned to find anti-viral potential of 2500 flavonoids inhibitors against the DENVNS2B/NS3 protease through computational screening which can hinder the viral replication within the host cell. By using molecular docking, it was revealed that flavonoids showed strong and stable bonding in the binding pocket of DENV NS2B/NS3 protease and had strong interactions with catalytic triad. Drug capability and anti-dengue potential of the flavonoids was also evaluated by using different bioinformatics tools. Some flavonoids effectively blocked the catalytic triad of DENV NS2B/NS3 protease and also passed through drug ability evaluation. It can be concluded from this study that these flavonoids could act as potential inhibitors to stop the replication of DENV and there is a need to study the action of these molecules in-vitro to confirm their action and other properties.