TAILIEUCHUNG - Báo cáo y học: " Characterization of thiobarbituric acid derivatives as inhibitors of hepatitis C virus NS5B polymerase"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Characterization of thiobarbituric acid derivatives as inhibitors of hepatitis C virus NS5B polymerase | Lee et al. Virology Journal 2011 8 18 http content 8 1 18 J VIROLOGY JOURNAL SHORT REPORT Open Access Characterization of thiobarbituric acid derivatives as inhibitors of hepatitis C virus NS5B polymerase Jong-Ho Lee Sangyoon Lee Mi Young Park Heejoon Myung Abstract In an effort to find chemicals inhibiting the enzymatic activity of the hepatitis C virus HCV NS5B polymerase a series of thiobarbituric acid derivatives were selected from a library provided by Korea Research Institute of Chemical Technology and characterized. The selected compounds exhibited IC50 values ranging from to pM and EC50 values ranging from to pM against NS5B polymerase of type 1b strain. They showed little effect against type 2a polymerase. One of the compounds G05 was selected and further characterized. It inhibited the synthesis of RNA by recombinant HCV NS5B polymerase in a dose dependent manner. The CC50 value was 77 pM. The inhibition was in a noncompetitive manner with the substrate UTP. The compound did not inhibit the elongation step of RNA synthesis in a single-cycle processive polymerization assay. It inhibited the binding of NS5B polymerase to the template RNA in a dose-dependent manner. Findings The hepatitis C virus causes chronic hepatitis in human and an estimated 170 million people are infected worldwide 1 2 . However no vaccine has yet been successful and no specific inhibitor is currently available other than interferon alpha and ribavirin where the response rate is lower than 50 and side effects have been reported 3 4 . Nonstructural protein 5B is responsible for HCV genomic replication 5 6 which made it a major target for the development of an antiviral therapy and many compounds have been reported to inhibit this target. Non-nucleoside inhibitors NNIs bind to an allosteric site and c ause a change in the conformation of the active site in the enzyme thereby inhibiting the initiation step whereas pyrophosphate mimics bind to catalytic

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