Research Unit, Shanghai Public Health Clinical Center, Caolang Road 2901, Shanghai 201508, China.
World J Gastroenterol. 2010 Jan 14;16(2):201-9. doi: 10.3748/wjg.v16.i2.201.
To evaluate the suitability of rupintrivir against Enterovirus 71 (EV71) induced severe clinical symptoms using computational methods.
The structure of EV71 3C protease was predicted by homology modeling. The binding free energies between rupintrivir and EV71 3C and human rhinovirus 3C protease were computed by molecular dynamics and molecular mechanics Poisson-Boltzmann/surface area and molecular mechanics generalized-born/surface area methods. EV71 3C fragments obtained from clinical samples collected during May to July 2008 in Shanghai were amplified by reverse-transcription and polymerase chain reaction and sequenced.
We observed that rupintrivir had favorable binding affinity with EV71 3C protease (-10.76 kcal/mol). The variability of the 3C protein sequence in isolates of various outbreaks, including those obtained in our hospital from May to July 2008, were also analyzed to validate the conservation of the drug binding pocket.
Rupintrivir, whose safety profiles had been proved, is an attractive candidate and can be quickly utilized for treating severe EV71 infection.
通过计算方法评估 Rupintrivir 对肠道病毒 71（EV71）引起的严重临床症状的适用性。
通过同源建模预测 EV71 3C 蛋白酶的结构。通过分子动力学和分子力学泊松-玻尔兹曼/表面积和分子力学广义 Born/表面积方法计算 Rupintrivir 与 EV71 3C 和人鼻病毒 3C 蛋白酶之间的结合自由能。2008 年 5 月至 7 月在上海采集的临床样本中扩增并测序获得 EV71 3C 片段。
我们观察到 Rupintrivir 与 EV71 3C 蛋白酶具有良好的结合亲和力（-10.76kcal/mol）。还分析了包括我们医院 2008 年 5 月至 7 月获得的病毒株在内的不同暴发中 3C 蛋白序列的变异性，以验证药物结合口袋的保守性。
Rupintrivir 的安全性已得到证实，是一种有吸引力的候选药物，可用于快速治疗严重的 EV71 感染。
