Abstract
Membrane fusion is the central molecular event during the entry of enveloped viruses into cells. The critical agents of this process are viral surface proteins, primed to facilitate cell bilayer fusion. The important role of Dendritic-cell-specific ICAM3-grabbing non-integrin (DC-SIGN) in Dengue virus transmission makes it an attractive target to interfere with Dengue virus Propagation. Receptor mediated endocytosis allows the entry of virions due to the presence of endosomal membranes and low pH-induced fusion of the virus. DC-SIGN is the best characterized molecule among the candidate protein receptors and is able to mediate infection with the four serotypes of dengue virus (DENV). Unrestrained pair wise docking was used for the interaction of dengue envelope protein with DC-SIGN and monoclonal antibody 2G12. Pre-processed the PDB coordinates of dengue envelope glycoprotein and other candidate proteins were prepared and energy minimized through AMBER99 force field distributed in MOE software. Protein-protein interaction server, ZDOCK was used to find molecular interaction among the candidate proteins. Based on these interactions it was found that antibody successfully blocks the glycosylation site ASN 67 and other conserved residues present at DC-SIGN-Den-E complex interface. In order to know for certain, the exact location of the antibody in the envelope protein, co-crystallize of the envelope protein with these compounds is needed so that their exact docking locations can be identified with respect to our results.
Highlights
Developing world is victim of largest vector-borne viral disease burden caused by the four serotypes of dengue virus (DENV) [1] and 50–100 million cases are reported yearly
DENV belongs to flavivirus genus of the Flaviviridae family, including numerous other important human pathogens such as tick-borne encephalitis (TBE), yellow fever (YF), West Nile (WN) and Japanese encephalitis (JE) viruses [5]
The epitopes predicted by ABCpred database in dengue virus envelope protein are listed in Table 2 and shown in supplementary data (S Figure 1 in supplementary file 1)
Summary
Developing world is victim of largest vector-borne viral disease burden caused by the four serotypes of dengue virus (DENV) [1] and 50–100 million cases are reported yearly. A greater risk for dengue hemorrhagic fever or dengue shock syndrome (DHF/DSS) is associated with different DENV serotype virus infection in the long term [4]. Viral uptake can be mediated by the presence of serotype cross-reactive and weakly neutralizing antibodies which enhance the infection of cells which bear Fcc receptors; this phenomenon is termed as antibodydependent enhancement (ADE) of infection. DENV belongs to flavivirus genus of the Flaviviridae family, including numerous other important human pathogens such as tick-borne encephalitis (TBE), yellow fever (YF), West Nile (WN) and Japanese encephalitis (JE) viruses [5]. Subsequent evidence from molecular data reaffirmed this classification and provided a clearer understanding of the phylogeny of the four serotypes: among the dengue viruses, DENV-4 diverged first from the common ancestor, followed by DENV-2, and DENV-1 and DENV-3 (figure 1) [6]
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