3D Modeling of dengue virus NS4B and Chikungunya virus nsP4: Identification of a common drug target and designing a single antiviral inhibitor
Autor(es): Satheesh Garisekurthi, Prabhu Nagu P, Venkataramana Musturi
Resumo: Dengue - chikungunya virus infections are one of the major causes of morbidity - mortality in tropical - sub-tropical regions of the world. These two viruses belong to two different families with many similarities - dissimilarities. Both are enveloped viruses - the mode of transmission is also by the same mosquito species. Especially in case of symptom expression, there is confusion between these two viruses. Reports indicate the overlapping endemic areas - co-infections of both viruses in a single patient. The above factors indicate that there is a need for developing a single drug/vaccine for both the viruses. As a first report in this direction, we have used the bioinformatics tools to identify a common target in both the viruses for a single inhibitor molecule. Phylogenetic - distance based analyses using the nucleotide sequences of arthropod - non-arthropod borne viruses indicated a common origin of evolutionary point for mosquito borne viruses, irrespective of their families. Similarly, the amino acid sequences of non-structural protein-4B (NS4B) of dengue virus - non-structural protein-P4 (nsP4) of chikungunya virus showed a common evolutionary origin. Modeled - superimposed 3D-structures of above two proteins showed a common alpha helix. Virtual screening of selected molecules was done to identify the molecules which can bind to the identified common helix - found that N-(p-tolylmethyl)-3-[(3-pyridylmethylamino)methyl]benzamide (TPB) has significant binding characteristics to the common helix. Molecular simulations indicated that both the protein-TPB complexes were stable. Therefore, we propose that TPB or its analogues could act as antiviral agents against both the viruses.
Palavras-Chave: 3D modeling; Chikungunya virus; Dengue virus; nsP4; Flavivirdae; Togaviridae; MD simulations; Molecular docking; NS4B
Imprenta: Current Computer-Aided Drug Design, v. 10, n. 4, p. 361-373, 2014
Identificador do objeto digital: 10.2174/1573409911666150407161535
Descritores: Chikungunya virus - Flaviviridae ; Chikungunya virus - Molecular structure ; Chikungunya virus - Proteins ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Molecular screening ; Chikungunya virus - Transmission ; Chikungunya virus - Vaccine ; Chikungunya virus - Dengue
Data de publicação: 2014
