Rupintrivir is a promising candidate for treating severe cases of Enterovirus-71 infection.
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.
Zhang
Xiao-Nan
XN
Research Unit, Shanghai Public Health Clinical Center, Caolang Road 2901, Shanghai 201508, China.
Song
Zhi-Gang
ZG
Jiang
Ting
T
Shi
Bi-Sheng
BS
Hu
Yun-Wen
YW
Yuan
Zheng-Hong
ZH
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
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