title: Identification of structural motifs in the E2 glycoprotein of Chikungunya involved in virus-host interaction.
abstract: Chikungunya fever is one of the reemerging vector-borne diseases. It has become a major global health problem especially in the developing countries. There are no vaccines or specific antiviral drugs available to date. This study reports small molecule inhibitors of envelope glycoprotein 2 (E2 glycoprotein) which are predicted based on Chikungunya virus-host interactions. E2 glycoprotein of Chikungunya virus interacts at 216 residue of the host receptor protein which plays a vital role in initiating infection. Understanding the structural aspects of E2 glycoprotein is crucial to develop specific inhibitors to prevent the virus binding from host receptors. In silico method was adopted to predict the sequence motifs of envelope protein, as the method like yeast two hybrid system is laborious, time consuming, and costly. The E2 glycoprotein structure of the Indian isolate was modeled using two templates (2XFC and 3JOC) and then validated. The class III PDZ domain binding motif was found to be identified at 213-216 amino acids. The corresponding peptide structures which recognize the PDZ domain binding motif were identified by the literature search and were used for generating five point pharmacophore model (ADDDR) containing acceptor, donor and aromatic ring features. Databases such as Asinex, TosLab and Maybridge were searched for the matches for the predicted pharmacophore model. Two compounds were identified as lead molecules as their glide score is > 5 kcal/mol. Since the pharmacophore model is developed based on Chikungunya virus-host interaction, it can be used for designing promising antiviral lead compounds for the treatment of Chikungunya fever.An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:21.
authors.affiliation: a PG & Research Department of Zoology and Biotechnology , Lady Doak College , Madurai , India.
authors.forename: J
authors.initials: J
authors.lastname: Asnet Mary
authors.forename: R
authors.initials: R
authors.lastname: Paramasivan
authors.forename: B K
authors.initials: BK
authors.lastname: Tyagi
authors.forename: M
authors.initials: M
authors.lastname: Surender
authors.forename: R
authors.initials: R
authors.lastname: Shenbagarathai
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002646:Chikungunya virus / Q000378:metabolism*; D018360:Crystallography, X-Ray; D054884:Host-Pathogen Interactions; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D016415:Sequence Alignment; D013379:Substrate Specificity; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D010455:Peptides; D014759:Viral Envelope Proteins