Zhang XN, Song ZG, Jiang T, Shi BS, Hu YW, Yuan ZH. Rupintrivir is a promising candidate for treating severe cases of Enterovirus-71 infection. World J Gastroenterol 2010; 16(2): 201-209 [PMID: 20066739 DOI: 10.3748/wjg.v16.i2.201]
Corresponding Author of This Article
Zheng-Hong Yuan, Professor, Research Unit, Shanghai Public Health Clinical Center, Caolang Road 2901, Shanghai 201508, China. zhyuan@shaphc.org
Article-Type of This Article
Original Article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Xiao-Nan Zhang, Zhi-Gang Song, Ting Jiang, Yun-Wen Hu, Zheng-Hong Yuan, Research Unit, Shanghai Public Health Clinical Center, Caolang Road 2901, Shanghai 201508, China
Bi-Sheng Shi, Zheng-Hong Yuan, Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University Dongan Road 130, Shanghai 200032, China
Author contributions: Zhang XN performed the majority of experiments and molecular simulations; Song ZG provided cDNA samples of EV71 infected patients; Jiang T performed phylogenetic analyses; Shi BS performed the cloning and sequencing of EV71 3C protease fragments; Hu YW and Yuan ZH coordinated and helped design the project.
Supported by Start-up Fund (No. KSF0062) of the Shanghai Public Health Clinical Center
Correspondence to: Zheng-Hong Yuan, Professor, Research Unit, Shanghai Public Health Clinical Center, Caolang Road 2901, Shanghai 201508, China. zhyuan@shaphc.org
Telephone: +86-21-64161928 Fax: +86-21-64227201
Received: October 7, 2009 Revised: November 8, 2009 Accepted: November 15, 2009 Published online: January 14, 2010
Abstract
AIM: To evaluate the suitability of rupintrivir against Enterovirus 71 (EV71) induced severe clinical symptoms using computational methods.
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.
RESULTS: 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.
CONCLUSION: Rupintrivir, whose safety profiles had been proved, is an attractive candidate and can be quickly utilized for treating severe EV71 infection.
