title: Structure based design towards the identification of novel binding sites and inhibitors for the chikungunya virus envelope proteins.
abstract: Chikungunya virus is an emerging arbovirus that is widespread in tropical regions and is spreading quickly to temperate climates with recent epidemics in Africa, Asia, Europe and the Americas. It is having an increasingly major impact on humans with potentially life-threatening and debilitating arthritis. Thus far, neither vaccines nor medications are available to treat or control the virus and therefore, the development of medicinal chemistry is a vital and immediate issue that needs to be addressed. The viral envelope proteins play a major role during infection through mediation of binding and fusion with the infected cell surfaces. The possible binding target sites of the chikungunya virus envelope proteins have not previously been investigated; we describe here for the first time the identification of novel sites for potential binding on the chikungunya glycoprotein complexes and the identification of possible antagonists for these sites through virtual screening using two successive docking scores; FRED docking for fast precise screening, with the top hits then subjected to a ranking scoring using the AUTODOCK algorithm. Both the immature and the mature forms of the chikungunya envelope proteins were included in the study to increase the probability of finding positive and reliable hits. Some small molecules have been identified as good in silico chikungunya virus envelope proteins inhibitors and these could be good templates for drug design targeting this virus.
authors.affiliation: Centre for Medicinal Chemistry, School of Chemistry, University of Wollongong, Wollongong 2522, Australia.
authors.forename: Adel A
authors.initials: AA
authors.lastname: Rashad
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keller
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002646:Chikungunya virus / Q000737:chemistry*; D003198:Computer Simulation; D015195:Drug Design; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D014759:Viral Envelope Proteins
keywords: Alphaviruses; Chikungunya virus; Envelope proteins; Virtual screening