Table 2.

HCV NS5B nucleoside and nucleoside analog pyrophosphorolysis parameters

Shown is a summary of kinetic parameters for pyrophosphorolysis of incorporated nucleosides and nucleoside analogs. The rate constants were derived by fitting the data sets using Scheme 1. S.E. values were derived by nonlinear regression in globally fitting the data (19). Confidence contour analysis supported the use of S.E. estimates derived from nonlinear regression.

Nucleotide	1/K1	k2	K1 k2	k−2	K3	k−2/K3 × 10−6
	μm	s−1	μm−1 s−1	s−1	μm	μm−1s−1
CTP	21 ± 1	46 ± 4	0.46 ± 0.05	0.3 ± 0.03	410 ± 50	730 ± 100
2′C-Me-CTP	1.7 ± 0.2	54 ± 7	0.032 ± 0.006	0.4 ± 0.04	820 ± 100	460 ± 83
2′C-Me-2′F-CTP	1.8 ± 0.2	56 ± 7	0.031 ± 0.006	0.3 ± 0.03	1600 ± 200	180 ± 24
UTP	28 ± 5	310 ± 70	0.09 ± 0.02	0.007 ± 0.002	1700 ± 200	4.1 ± 1
2′C-Me-2′F-UTP	410a	0.3a	0.00073a			≤0.01

^a Rate constants for 2′C-Me-2′F-UTP incorporation are from Table 2.