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The best approach for the development of a vaccine against a specific infection or a microbial disease is Insilico vaccine designing that is not only accurate but also requires minimum time, labour and economy. This approach can also be used to analyze the target structures for possible binding/active sites, generate candidate molecules, check for their drug likeness, dock these molecules with the target, rank them according to their binding affinities, further optimize the molecules to improve binding characteristics. During vaccine designing the disease to be selected should be a viral or a bacterial disease but not due to a protozoan, as they cannot be attenuated and injected. The main goal of the current work is to develop a vaccine against the disease Ebola. Computational tools offer the advantage of delivering new drug candidates more quickly and at a lower cost. This review provides succinct overview of several methods in drug discovery by using insilico approaches on identifying drug targets where there are genes or proteins associated with specific diseases.
Ebola, protein-protein BLAST, PVS tool, insilico methods, Zaire ebolavirus
Ebolavirus is a virological taxon included in the family Filoviridae, order Mononegavirales. It is a disease of humans and other primates caused by ebolaviruses. The disease has a high risk of death, killing between 25 and 90 percent of those infected, with an average of about 50 percent. [Kuhn J. H. et al, 2010] The Ebola virus (EBOV) protein VP24 inhibits type I and II interferon (IFN) signaling by binding to NPI-1 subfamily karyopherin α (KPNA) nuclear import proteins, preventing their interaction with tyrosine-phosphorylated STAT1 (phospho-STAT1). This inhibits phospho-STAT1 nucleaimport. A biochemical screen now identifies heterogeneous nuclear ribonuclear protein complex C1/C2 (hnRNP C1/C2) nuclear import as an additional target of VP24. Co-immunoprecipitation studies demonstrate that hnRNP C1/C2 interacts with multiple KPNA family members, including KPNA1. Interaction with hnRNP C1/C2 occurs through the same KPNA1 C-terminal region (amino acids 424–457) that binds VP24 and phospho-STAT1. The ability of hnRNP C1/C2 to bind KPNA1 is diminished in the presence of VP24, and cells transiently expressing VP24 redistribute hnRNP C1/C2 from the nucleus to the cytoplasm. These data further define the mechanism of hnRNP C1/C2 nuclear import and demonstrate that the impact of EBOV VP24 on nuclear import extends beyond STAT1. [Isaacson M. et al, 1976] The five characterized species of the Ebolavirus genus are Zaire ebolavirus, Sudan ebolavirus, Reston ebolavirus, Taï Forest ebolavirus and Bundibugyo ebolavirus. [Feldmann H. et al, 2005] The species Zaire ebolavirus is a virological taxon. The species has a single virus member, Ebola virus The species was introduced in 1998 as Zaire Ebola virus. In 2002, the name was changed to Zaire ebolavirus. It has a genomic sequence that differs from the type virus by less than 30%. [Mayo M. A. et al, 2002]
In vaccine designing the user is working on the complete proteome of the selected pathogenic virus. We have selected the organism as Zaire ebolavirus. Once the proteome is downloaded the next step is to remove all the proteins that are Predicted, Hypothetical, Unnamed or Putative. Then the selected proteins must be screened for the Foreignness based on the tool BlastP. In BlastP all the foreign peptides can be selected which can be further processed to Antigenic Peptide Prediction Using Protein Verification Server tool. Based on the results of PVS, best peptides having maximum Antigenic Propensity can be selected. From all the peptides selected based on PVS, SAA calculation must be performed to detect the best peptide having both antigenicity and accessibility to the external ligand. The Highest peaks were found to be 171-183 and 239-271Antigenic peptide = KLRALLTLCAVMT and SLIMFITAFLNIALQLPCESSAVVVSGLRTLVP The selected peptides are designed in Argus lab and they are optimized followed by their energy Calculation. Finally the peptide that has maximum SAA, Foreignness and Minimum energy can be selected as the Best Vaccine candidate. The peptide with maximum SAA and minimum total energy is KLRALLTLCAVMT which can be further used to develop vaccine against the disease Ebola.
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