Antiviral mechanism of pyrazolo [3,4-d] pyrimidines to enterovirus 71

• Main Authors: Pei-Fen Lin, 林佩芬
• Other Authors: Shin-Ru Shih
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/16030944589074113283

碩士 === 長庚大學 === 醫學生物技術研究所 === 93 === Enterovirus 71 is one of the most important pathogens in the family of Picornaviridae that can cause severe complications in the postpoliovirus era, such as encephalitis, pulmonary edema, and even death. Pyrazolo [3,4-d] pyrimidine is a novel class of potent and selective human enterovirus 71 inhibitor. BPR1D041SO, one of Pyrazolo [3,4-d] pyrimidines, was used to investigate the antiviral mechanism to enterovirus 71. Time course experiments revealed that BPR1D041SO effectively inhibited virus replication not only in the early stage but in the later stage about one to four hours of post infection. This may suggest that the drug targeted to steps involved in RNA translation, protein processing, or RNA replication. BPR1D041SO was used to select and characterize the drug-resistant virus. Sequence analyses of full viral genome have been performed. The data showed that the resistant variants differed consistently by one nucleotide and eight amino acids from their parental drug-sensitive strain. There were nucleotide—G656A in 5’UTR, amino acids—G99S, T100I, Y106C, Q149L, and P243S in VP1, T256A in 2C, and R163K, S264L in 3D. These mutations may responsible for the drug-resistant phenotype.