Structure based design towards the identification of novel binding sites and inhibitors for the Chikungunya virus envelope proteins
Autor(es): Rashad Adel A, Keller Paul A
Resumo: Chikungunya virus is an emerging arbovirus that is widespread in tropical regions - is spreading quickly to temperate climates with recent epidemics in Africa, Asia, Europe - the Americas. It is having an increasingly major impact on humans with potentially life-threatening - debilitating arthritis. Thus far, neither vaccines nor medications are available to treat or control the virus - therefore, the development of medicinal chemistry is a vital - immediate issue that needs to be addressed. The viral envelope proteins play a major role during infection through mediation of binding - 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 - 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 - the mature forms of the chikungunya envelope proteins were included in the study to increase the probability of finding positive - reliable hits. Some small molecules have been identified as good in silico chikungunya virus envelope proteins inhibitors - these could be good templates for drug design targeting this virus.
Palavras-Chave: Alphaviruses; Chikungunya virus; Envelope proteins; Virtual screening
Imprenta: Journal of Molecular Graphics & Modelling, v. 44, p. 241-252, 2013
Identificador do objeto digital: 10.1016/j.jmgm.2013.07.001
Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Molecular structure ; Chikungunya virus - Proteins ; Chikungunya Virus - Virus ; Chikungunya virus - Molecular screening ; Chikungunya virus - Vaccine ; Chikungunya virus - Epidemic
Data de publicação: 2013
