Autor(es): Rungrotmongkol Thanyada, Nunthaboot Nadtanet, Malaisree Maturos, Kaiyawet Nopporn, Yotmanee Pathumwadee, Meeprasert Arthitaya, Hannongbua Supot

Resumo: The outbreaks of chikungunya (CHIKV) - venezuelan equine encephalitis (VEEV) viral infections in humans have emerged or re-emerged in various countries of Africa - southeast Asia", - "central - south America", respectively. At present, no drug or vaccine is available for the treatment - therapy of both viral infections, but the non-structural protein, nsP3, is a potential target for the design of potent inhibitors that fit at the adenosine-binding site of its macro domain. Here, so as to underst- the fundamental basis of the particular interactions between the ADP-ribose bound to the nsP3 amino acid residues at the binding site, molecular dynamics simulations were applied. The results show that these two nsP3 domains share a similar binding pattern for accommodating the ADP-ribose. The ADP-ribose phosphate unit showed the highest degree of stabilization through hydrogen bond interactions with the nsP3 V33 residue - the consequent amino acid residues 110-114. The adenine base of ADP-ribose was specifically recognized by the conserved nsP3 residue D10. Additionally, the ribose - the diphosphate units were found to play more important roles in the CHIKV nsP3-ADP-ribose complex, while the ter-ribose was more important in the VEEV complex. The slightly higher binding affinity of ADP-ribose toward the nsP3 macro domain of VEEV, as predicted by the simulation results, is in good agreement with previous experimental data. These simulation results provide useful information to further assist in drug design - development for these two important viruses."

Palavras-Chave: Chikungunya; Venezuelan equine encephalitis; ADP-ribose; Molecular dynamics simulations

Imprenta: Journal of Molecular Graphics & Modelling, v. 29, n. 3, p. 347-53, 2010

Identificador do objeto digital: 10.1016/j.jmgm.2010.09.010

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine

Data de publicação: 2010