title: Rupintrivir is a promising candidate for treating severe cases of Enterovirus-71 infection.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Rupintrivir, whose safety profiles had been proved, is an attractive candidate and can be quickly utilized for treating severe EV71 infection.
authors.affiliation: Research Unit, Shanghai Public Health Clinical Center, Caolang Road 2901, Shanghai 201508, China.
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Zhang
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Song
authors.forename: Ting
authors.initials: T
authors.lastname: Jiang
authors.forename: Bi-Sheng
authors.initials: BS
authors.lastname: Shi
authors.forename: Yun-Wen
authors.initials: YW
authors.lastname: Hu
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Yuan
mesh_terms: D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000737:chemistry; D029821:Enterovirus A, Human / Q000201:enzymology; D004769:Enterovirus Infections / Q000188:drug therapy*; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011760:Pyrrolidinones / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D014764:Viral Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D007555:Isoxazoles; D011480:Protease Inhibitors; D011760:Pyrrolidinones; D014764:Viral Proteins; D010649:Phenylalanine; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; D014633:Valine; C118874:rupintrivir