Figure 5.

HRV-16 or EV-71 RdRp-catalyzed RNA synthesis and pattern of inhibition following a single incorporation of ATP or GS-646939 as a function of nucleotide concentration. A, RNA primer/template supporting RNA synthesis and a single incorporation of ATP or GS-646939 at position 6 (“i”). G indicates incorporation of [α-³²P]-GTP at position 5. B, migration pattern of RNA products resulting from HRV-16 RdRp-catalyzed RNA extension of AMP (left) of GS-646939 (right) at increasing concentrations of CTP and UTP. A 5′-³²P-labeled 4-nt primer serves as a size marker. Product formation at and beyond the asterisk indicates RNA products that are likely a result of sequence-dependent slippage events. C, RNA synthesis products catalyzed by EV-71 RdRp. Incomplete inhibition of RNA synthesis occurs at the site of GS-646939 incorporation (“i”), full template-length product is generated at elevated nucleotide concentrations. EV-71, enterovirus 71; HRV, human rhinovirus; RdRp, RNA-dependent RNA polymerase.