Immunoinformatics and Immunogenetics-Based Design of Immunogenic Peptides Vaccine against the Emerging Tick-Borne Encephalitis Virus (TBEV) and Its Validation through In Silico Cloning and Immune Simulation.

Pegivirus, HPgV, earlier known as Gb virus and hepatitis G virus, is an enveloped, positive-stranded RNA and lymphotropic virus classified into the Flaviviridae family. The transmission routes primarily involve blood products, with infections worldwide, leading up to 25% of persistent infections. To date, no effective therapeutic means are available to resolve Pegivirus infections. Effective vaccine therapeutics are the best alternative to manage this disease and any associated potential pandemic. Thus, whole proteome-based mining of immunogenic peptides, i.e., CTL (cytotoxic T lymphocytes), HTL (helper T lymphocytes) and B cell epitopes were mapped to design a vaccine ensemble. Our investigation revealed that 29 different epitopes impart a critical role in immune response induction, which was also validated by exploring its physiochemical properties and experimental feasibility. In silico expression and host immune simulation using an agent-based modeling approach confirmed the induction of both primary and secondary immune factors such as IL, cytokines and antibodies. The current study warrants further lab experiments to demonstrate its efficacy and safety.

Characterization of a novel cotton MYB gene, GhMYB108-like responsive to abiotic stresses.

Transcriptional factors are the major regulators of plant signaling pathways in response to environmental stresses i.e., drought, salinity and cold. Hereby, the GhMYB108-like was characterized to determine whether it regulate these stresses. The GhMYB108-like cDNA consisted of 1107 base pairs (bp) with 807 open reading frame encoded a protein of 268 amino acids. Its isoelectric point and molecular weight are 5.51 and 30.3 kDa respectively. Phylogenetic analysis and online databases revealed that GhMYB108-like proteins are closely related with the Arabidopsis thaliana MYB2. Important cis-elements were detected in the promotor region of GhMYB108-like responding to stresses and phytohormones. The 3D structure of GhMYB108-like protein has been predicted. In addition, various physico-chemical properties of GhMYB108-like have been determined. Subcellular localization confirmed that GhMYB108-like are nuclear localized protein. Quantitative expression analysis showed that polyethylene glycol and salt treatments significantly induced the expression of GhMYB108-like. Overall, our findings suggest that GhMYB108-like is an important gene that would plays important regulatory role in response to drought and salt stresses.

A chemosensory protein MsepCSP5 involved in chemoreception of oriental armyworm Mythimna separata.

Chemosensory proteins (CSPs) have been suggested to perform several functions in insects, including chemoreception. To find out whether MsepCSP5 identified from Mythimna separata shows potential physiological functions in olfaction, gene expression profiles, ligand-binding experiments, molecular docking, RNA interference, and behavioral test were performed. Results showed that MsepCSP5 was highly expressed in female antennae. MsepCSP5 showed high binding affinities to a wide range of host-related semiochemicals, and displayed that 26 out of 35 candidate volatiles were highly bound (Ki < 10 µM) at pH 5.0 rather than pH 7.4. The binding sites of MsepCSP5 to candidate volatiles were well predicted by three-dimensional structure modeling and molecular docking experiments. Pursuing further, biological activities of M. separata to highly bound compounds elicited strong behavioral responses, such as alcoholic compounds displayed strong attractiveness whereas terpenes showed repellency to M. separata. The transcript expression level of MsepCSP5 gene significantly decreased after injecting target dsRNAs, and resulted in non-significant preference responses of M. separata to semiochemicals, such as 3-pentanol and 1-octene-3-ol. In conclusion, MsepCSP5 may involve in semiochemical reception of M. separata.

The critical role of p16/Rb pathway in the inhibition of GH3 cell cycle induced by T-2 toxin.

T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2 toxin is involved in G1 phase arrest in several cell lines but molecular mechanism is still not clear. In present study, we used rat pituitary GH3 cells to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40 nM) for 12, 24, 36 and 48 h as compared to control cells. GH3 cells showed a considerable increase in reactive oxygen species (ROS) as well as loss in mitochondrial membrane potential (△Ym) upon exposure to the T-2 toxin. Flow cytometry showed a significant time-dependent increase in percentage of apoptotic cells and gel electrophoresis showed the hallmark of apoptosis oligonucleosomal DNA fragmentation. Additionally, T-2 toxin-induced oxidative stress and DNA damage with a time-dependent significant increased expression of p53 favors the apoptotic process by the activation of caspase-3 in T-2 toxin treated cells. Cell cycle analysis by flow cytometry revealed a time-dependent increase ofG1 cell population along with the significant time-dependent up-regulation of mRNA and protein expression of p16 and p21 and significant down-regulation of cyclin D1, CDK4, and p-RB levels further verify the G1 phase arrest in GH3 cells. Morphology of GH3 cells by TEM clearly showed the damage and dysfunction to mitochondria and the cell nucleus. These findings for the first time demonstrate that T-2 toxin induces G1 phase cell cycle arrest by the involvement of p16/Rb pathway, along with ROS mediated oxidative stress and DNA damage with p53 and caspase cascade interaction, resulting in apoptosis in GH3 cells.

MPD3: a useful medicinal plants database for drug designing.

Medicinal plants are the main natural pools for the discovery and development of new drugs. In the modern era of computer-aided drug designing (CADD), there is need of prompt efforts to design and construct useful database management system that allows proper data storage, retrieval and management with user-friendly interface. An inclusive database having information about classification, activity and ready-to-dock library of medicinal plant's phytochemicals is therefore required to assist the researchers in the field of CADD. The present work was designed to merge activities of phytochemicals from medicinal plants, their targets and literature references into a single comprehensive database named as Medicinal Plants Database for Drug Designing (MPD3). The newly designed online and downloadable MPD3 contains information about more than 5000 phytochemicals from around 1000 medicinal plants with 80 different activities, more than 900 literature references and 200 plus targets. The designed database is deemed to be very useful for the researchers who are engaged in medicinal plants research, CADD and drug discovery/development with ease of operation and increased efficiency. The designed MPD3 is a comprehensive database which provides most of the information related to the medicinal plants at a single platform. MPD3 is freely available at: http://bioinform.info .

Prediction of Protein-Protein Interactions by Evidence Combining Methods.

Most cellular functions involve proteins' features based on their physical interactions with other partner proteins. Sketching a map of protein-protein interactions (PPIs) is therefore an important inception step towards understanding the basics of cell functions. Several experimental techniques operating in vivo or in vitro have made significant contributions to screening a large number of protein interaction partners, especially high-throughput experimental methods. However, computational approaches for PPI predication supported by rapid accumulation of data generated from experimental techniques, 3D structure definitions, and genome sequencing have boosted the map sketching of PPIs. In this review, we shed light on in silico PPI prediction methods that integrate evidence from multiple sources, including evolutionary relationship, function annotation, sequence/structure features, network topology and text mining. These methods are developed for integration of multi-dimensional evidence, for designing the strategies to predict novel interactions, and for making the results consistent with the increase of prediction coverage and accuracy.

Antiviral phytochemicals identification from Azadirachta indica leaves against HCV NS3 protease: an in silico approach.

Hepatitis C virus (HCV) is a major health problem across the world affecting the people of all age groups. It is the main cause of hepatitis and at chronic stage causes liver cirrhosis and hepatocellular carcinoma. Various therapeutics are made against HCV but still there is a need to find out potential therapeutics to combat the virus. The goal of this study is to identify the phytochemicals of Azadirachta indica leaves having antiviral activity against HCV NS3 protease through molecular docking and simulation approach. Results show that the compound 3-Deacetyl-3-cinnamoyl-azadirachtin possesses good binding properties with HCV NS3/4A protease. It can be concluded from this study that Deacetyl-3-cinnamoyl-azadirachtin may serve as a potential inhibitor against NS3/4A protease.