Ibicuruzwa

Beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) ni ikintu gikomeye cyangiza virusi ya hepatite C (HCV) RNA mu ngirabuzimafatizo za Huh-7.Kugirango uhagarike polymerase ya HCV NS5B RNA, PSI-6130 igomba kuba fosifora muburyo bwa 5'-triphosifate.Hakozwe iperereza kuri fosifora ya PSI-6130 no kubuza HCV NS5B.Fosifora ya PSI-6130 na recombinant muntu 2'-deoxycytidine kinase (dCK) na uridine-cytidine kinase 1 (UCK-1) yapimwe hakoreshejwe reaction ya spekitifoto.PSI-6130 yerekanwe ko ari substrate ya dCK isukuye, ifite Km ya microM 81 na kcat ya 0.007 s-1, ariko ntabwo yari substrate ya UCK-1.PSI-6130 monophosphate (PSI-6130-MP) yashizwemo fosifori neza na diphosphate hanyuma ikurikirwa na triphosphate na recombinant muntu UMP-CMP kinase na nucleoside diphosphate kinase.Kubuza ubwoko bwa gasozi kandi bwahinduwe (S282T) HCV NS5B RNA polymerase.Guhagarika-guhagarikwa kwa leta (Ki) kuri PSI-61 30 triphosifate (PSI-6130-TP) hamwe na enzyme yo mu gasozi yari microM 4.3.Ibisubizo nkibi byabonetse hamwe na 2'-C-methyladenosine triphosphate (Ki = 1.5 microM) na 2'-C-methylcytidine triphosphate (Ki = 1,6 microM).NS5B hamwe na S282T ihindagurika, izwiho gutanga imbaraga zo kurwanya 2'-C-methyladenosine, yabujijwe na PSI-6130-TP neza nkubwoko bwishyamba.Kwinjiza PSI-6130-MP muri RNA itangizwa na NS5B RNA polymerase isukuye byatumye iminyururu irangira.