Mosquito-borne flaviviruses (MBFVs) are important cause of emerging and re-emerging human diseases nearly worldwide, transmitted by arthropod vectors (mostly aedes and culex mosquitoes), with particular reference to yellow fever virus, Japanese encephalitis virus, dengue fever virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, etc. In over 100 countries, more than 2.5 billion people are at risk of infection, and approximately 20 million infections are reported annually. Through the analysis of gene sequence data of these virus populations it is possible to infer phylogenetic relationships, which in turn can yield important epidemiological information, including their demographic history. Early attempts to define the evolutionary relationships and origins of viruses in the genus flavivirus are hampered by the lack of genetic information particularly amongst the MBFVs. In this study, complete genome, translated polyprotein, structural and non-structural proteins of MBFVs have been targeted and revealed an extensive series of clades defined by their epidemiology and disease associations. The branching patterns of at the deeper nodes of the resultant trees were different from those reported in the previous study. The significance of these observations is discussed.

BackgroundThe small delta antigen protein of hepatitis delta virus (HDV) has been shown to be important for replication of the virus and essential for the viral life cycle. Therefore, it may be an appropriate target for designing biological experiments for drug development to identify the potential inhibitors of hepatitis D.ObjectivesTo identify a novel molecule as possible drug candidate for the treatment of Hepatitis D.Materials and MethodsIn the present study, a computational approach was used for the identification of novel small-molecule inhibitors against HDV replication using docking studies. An Autodock tool was used for docking and identifying the active binding sites in target proteins. The Lipinski filter and preADMET program were also used for determining the pharmacokinetic properties in order to filter out potential ligand molecules to restrain virus replication.ResultsOur results suggest that pyridinone (3-[(4,7-dichloro-1,3-benzoxazol-2-yl) methylamino]-5-ethyl-6-methyl-pyridin-2(1H)-one) is a validated potential inhibitor of HDV replication and could be as a novel antiviral drug for the treatment of hepatitis D.CounclusionsWe have identified a novel antiviral drug by using innovative computational approaches. The results provide a basis to experimentally develop into drug which can be used for the treatment of delta hepatitis.

Campylobacteriosis is a deadly disease which has developed resistance to most of the available chemotherapeutic agents. Although various studies provide evidence of acquired immunity following exposure to Campylobacter jejuni, no effective vaccine has been developed, still. Hence, there is an urgent need to identify potential vaccine candidates for Campylobacter species. In the proposed study, Campylobacter jejuni subsp. jejuni serotype O:2 (strain NCTC 11168) was taken and computational approach was employed to screen C. jejuni genome for promising vaccine candidates. From 1623 protein-coding sequences, 37 potential antigens were screened for epitope prediction based on surface association, consensus antigenicity predictions, solubility, transmembrane domain, and ortholog analysis. Comprehensive immunogenic analysis of these 37 antigens revealed that antigen Q0PA22 shows the greatest potential for experimental immunogenicity analysis. It has several potential CD4+ and CD8+ T-cell epitopes, as well as high probability of B-cell epitope regions as compared to well-characterized antigen Omp18 (Uniprot ID:Q0PC24). Among the highest scoring predicted epitopes, an optimal set of epitopes with respect to overall immunogenicity in target populations for campylobacteriosis viz. Europe, North America and Southwest Asia was determined. An epitope AMLTYMQWL from antigen no. 6(Q0PA22) binds to the most prevalent allele HLA-A*0201, and this epitope has most immunogenicity for all the target populations. In addition, this epitope exhibited highly significant TCR-pMHC interactions having a joint Z value of 4.87. Homology mapping studies of the predicted epitope show best homology to a well-studied antigenic peptide from influenza virus H5N1. Therefore, the predicted epitope might be a suitable vaccine candidate.

Japanese encephalitis (JE) is an acute central nervous system inflammatory disease caused by the Japanese encephalitis virus (JEV). JEV is a small, enveloped, plus-strand RNA virus belonging to the genus Flavivirus. In this study, envelope protein (E) that mediates the entry of JEV into host cell has been preferred as potential molecular target for drug development. The 3-D structure of E protein was designed and validated using modeler9.10 and procheck tool, respectively, and also optimized using molecular dynamics simulation. A number of lead molecules were used for computational virtual screening against JEV E protein. Three top ranked lead molecules with strong binding affinity to JEV E protein were identified based on minimum binding energy. Molecular dynamic simulation was also performed for protein-ligand complex to study the mobility of complex at various time intervals. Drug likeliness and comparative bioactivity analysis for these leads using OSIRIS Property Explorer had shown that these molecules would have the potential to act as better drug. The mycophenolate was found to be most suitable as entry inhibitor therapeutic molecule for JEV E protein, which may be considered as a potential ligand for treatment of Japanese encephalitis.

Geminiviruses are single-stranded circular DNA viruses causing leaf curl disease in papaya crop. Post-Transcriptional Gene Silencing (PTGS), also known as RNAi, acts as a natural antiviral defence mechanism and plays a role in genome maintenance and development in plants. PTGS suppression by viruses makes the plant RNA silencing machinery inefficient. Three geminiviral genes namely AV2, AC2 and AC4 are found to play the role in suppression of RNA silencing. siRNA degrades the target mRNA in a homology-dependent manner. In-silico designing of siRNA against these three genes of geminiviruses infecting Carica papaya was done using bioinformatics tools. This strategy may provide PTGS by specifically targeting the viral genes involved in suppression of plant RNA silencing machinery.