TABLE 2.
Kinetic parameters for nucleoside 5′-triphosphate incorporation by HCV NS5B polymerase
NTP substrate | Kd,appa (μM) | kpola (s−1) | Incorporation efficiencyb | Selectivityc |
---|---|---|---|---|
ATP | 1.4 ± 0.9 | 1.3 ± 0.6 | 0.9 | |
2′-C-Methyl-DAPN-TP | 37 ± 1.0 | 0.05 ± 0.02 | 0.001 | 900 |
GTP | 4.1 ± 1.6 | 4.1 ± 0.9 | 1.0 | |
2′-C-Methyl-GTP | 9.6 ± 1.9 | 0.7 ± 0.3 | 0.07 | 13.3 |
Kinetic parameters were calculated based on at least two separate replicates ± standard deviations (see Fig. 3 for additional information).
Incorporation efficiency was determined as kpol/Kd,app for each NTP.
Selectivity was determined as (kpol/Kd,app)NTP/(kpol/Kd,app)rNAI-TP.