Flavivirus membrane fusion
ABSTRACT Flavivirus membrane fusion is mediated by a class II viral fusion protein, the major envelope protein E, and the fusion process is extremely fast and efficient. Understanding of the underlying mechanisms has been advanced significantly by the determination of E protein structures in their pre- and post-fusion conformations and by the elucidation of the quarternary organization of E proteins in the viral envelope. In this review, these structural data are discussed in the context of functional and biochemical analyses of the flavivirus fusion mechanism and its characteristics are compared with those of other class II- and class I-driven fusion processes.
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ABSTRACT: Japanese Encephalitis (JE) is a vector- borne, viral zoonosis that may affect humans. The disease periodically becomes endemic in areas such as northern India, parts of central and southern India. Japanese Encephalitis virus belongs to the mostly vector-borne flaviviriade, which are single stranded RNA viruses. The envelope glycoprotein of JE Viruses contain specific as well as cross relative, neutralizing epitopes. The objective of this research to find out the best ligand molecule each for the two drug targeting protein present in the JEV. This will be done by studying the complete structure of JEV drug targeting proteins and their interaction with their respective ligand. The envelope protein and NS1 protein have been studied. The minimum energies were recorded after the docking studies for all the inhibitors docked with the protein. After comparison of the minimum energies recorded, the ligand with the least minimum docking energy has been considered as the best ligand. The entire study indicates that the inhibitor Mycophenolate with minimum energy -5.00605kj/mol is the most effective against Envelope protein. However in case of NS1 protein, the inhibitor Deoxynojirimycin with the minimum energy of - 6.75932kj/mol is found to be the most effective.International Journal of Applied Biology and Pharmaceutical Technology 03/2015; 6(2):126-131. · 0.99 Impact Factor
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ABSTRACT: The specific interactions of the pairs laminin binding protein (LBP)–purified tick-borne encephalitis viral surface protein E and certain recombinant fragments of this protein, as well as West Nile viral surface protein E and certain recombinant fragments of that protein, are studied by combined methods of single-molecule dynamic force spectroscopy (SMDFS), enzyme immunoassay and optical surface waves-based biosensor measurements. The experiments were performed at neutral pH (7.4) and acid pH (5.3) conditions. The data obtained confirm the role of LBP as a cell receptor for two typical viral species of the Flavivirus genus. A comparison of these data with similar data obtained for another cell receptor of this family, namely human αVβ3 integrin, reveals that both these receptors are very important. Studying the specific interaction between the cell receptors in question and specially prepared monoclonal antibodies against them, we could show that both interaction sites involved in the process of virus–cell interaction remain intact at pH 5.3. At the same time, for these acid conditions characteristic for an endosome during flavivirus–cell membrane fusion, SMDFS data reveal the existence of a force-induced (effective already for forces as small as 30–70 pN) sharp globule–coil transition for LBP and LBP–fragments of protein E complexes. We argue that this conformational transformation, being an analog of abrupt first-order phase transition and having similarity with the famous Rayleigh hydrodynamic instability, might be indispensable for the flavivirus–cell membrane fusion process. Copyright © 2014 John Wiley & Sons, Ltd.Journal of Molecular Recognition 12/2014; 27(12). DOI:10.1002/jmr.2399 · 2.34 Impact Factor
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ABSTRACT: Dengue is a vector borne viral disease which causes millions of death in the tropical regions. Entry of dengue virus is mediated by conformational change in envelope protein due to change in endosomal pH. The structural study of dengue envelope protein (DENV) reveals that domain-III of envelope protein exhibits largest conformational change during entry of virus. Hence, a drug which may block this conformational change will be relatively more effective. The present work aims to explore the hot spots and key interacting residues of some known drugs using molecular docking, molecular dynamic simulations and free energy calculations. We have explored the conformational changes in envelope protein in presence of different drugs and pointed out those residues which commonly participate in binding of all drugs. The binding of these drugs was calculated by free energy and molecular docking methods and their relative accuracy were also compared. We have found several amino acids commonly interacting to all five drugs. In addition, the results of molecular dynamic simulations were more reliable than molecular docking. The binding free energy of drug R1 is better than the other drugs which follows the experimental observations. The root mean square deviations for R1 are better than the other drugs which also supports a stable (less flexible) binding for this drug.BioMed Research International 09/2014; · 2.71 Impact Factor