| Summary: | 碩士 === 國立清華大學 === 分子醫學研究所 === 93 === It is estimated that there are 170 million chronically infected HCV carriers worldwide（2%~3% of the global population）. Within 20 years of infection, about 4~5% of them will develop cirrhosis and hepatocellular carcinoma, often resulting in death. Current HCV therapy consists of injectable, α-interferon used alone or in combination with ribavirin. Although effective in certain patient populations, interferon therapy has several limitations including high cost and significant side effects that often require does adjustment or discontinuation of therapy. Moreover, while not will understood, interferon therapy has been shown to be most effective against genotype 2 and 3 HCV infections and least effective against genotype 1 infections. The lack of an effective and well-tolerated treatment has therefore spurred intense research efforts to develop affordable, oral and novel anti-HCV agents.
We chose HCV genome type 1b as a drug target using the approach of virtual docking screening to find the potential drug candidates both of noncompetitive and nonnucleoside inhibitor binding site. According to the dimension of noncompetitive inhibitor, we had finished the task of drug screening, and screened out one hundred compounds whose ligands were different or not exactly different on orientation and binding site. Besides, we sorted those compounds from the best to the worst by the method of energy score and the numbers of pharmacophore to select the first fifty good ones and secondary fifty good ones by the calculating result. All above as we had mentioned are in the procedure of biotest. In another portion,the dimension of nonnucleoside inhibitor, we had also chosen one hundred compounds whose ligands were different or not exactly different on orientation and binding site to perform the biotest.
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