Sharma Rajesh, Kesari Pooja, Kumar Pravindra, Tomar Shailly
Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India.
Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India.
Virology. 2018 Feb;515:223-234. doi: 10.1016/j.virol.2017.12.020. Epub 2018 Jan 5.
The crystal structure of chikungunya (CHIKV) virus capsid protease domain has been determined at 2.2Å. Structure reveals a chymotrypsin-like protease fold with a conserved hydrophobic pocket in CHIKV capsid protein (CP) for interaction with the cytoplasmic tail of E2 (cdE2) similar to the capsid protein of other alphaviruses. Molecular contacts between CP-cdE2 were determined by fitting structures of CHIKV CP and cdE2 into the cryo-EM map of Venezuelan equine encephalitis virus (VEEV). Binding of (S)-(+)-Mandelic acid (MDA) and Ethyl 3-aminobenzoate (EAB) to the hydrophobic pocket of CP was evaluated by molecular docking. Surface plasmon resonance (SPR) and fluorescence spectroscopy experiments confirmed MDA and EAB binding to the CP. The binding constants (K) obtained from SPR for MDA and EAB were 1.2 × 10 M and 0.2 × 10 M, respectively. This study adds to the understanding of chikungunya virus structural proteins and may serve as the basis for antiviral development against chikungunya disease.
基孔肯雅病毒（CHIKV）衣壳蛋白酶结构域的晶体结构已在2.2埃分辨率下确定。结构显示其具有类似胰凝乳蛋白酶的蛋白酶折叠结构，在CHIKV衣壳蛋白（CP）中存在一个保守的疏水口袋，用于与E2的细胞质尾巴（cdE2）相互作用，这与其他甲病毒的衣壳蛋白类似。通过将CHIKV CP和cdE2的结构拟合到委内瑞拉马脑炎病毒（VEEV）的冷冻电镜图谱中，确定了CP-cdE2之间的分子接触。通过分子对接评估了（S）-（+）-扁桃酸（MDA）和3-氨基苯甲酸乙酯（EAB）与CP疏水口袋的结合情况。表面等离子体共振（SPR）和荧光光谱实验证实了MDA和EAB与CP的结合。从SPR获得的MDA和EAB的结合常数（K）分别为1.2×10 M和0.2×10 M。这项研究增进了对基孔肯雅病毒结构蛋白的理解，并可能为抗基孔肯雅病的抗病毒药物开发提供基础。
