TABLE 8.

Potencies of elbasvir in transiently expressed genotype 1a(H77) replicons bearing NS5A RAVs from resistant colonies

Variant	EC50, nMa	Fold shift vs WTb	Relative fitnessc
WT	0.007 ± 0.004	1	1
K24E	NTd	NT	Unfit
K24N	0.003 ± 0.002	0.4	0.1
K24R	0.007 ± 0.004	1	0.8
K24T	0.003 ± 0.002	0.4	0.9
M28T	0.11 ± 0.03	15	0.8
M28V	0.01 ± 0.01	1	1.0
Q30D	NT	NT	Unfit
Q30E	0.39 ± 0.02	56	0.9
Q30G	0.59 ± 0.31	84	0.7
Q30H	0.044 ± 0.03	6	1.3
Q30R	0.11 ± 0.009	16	0.8
L31 M	0.07 ± 0.03	10	1.5
L31V	0.43 ± 0.13	61	0.9
R81 M	0.005 ± 0.005	1	1.3
R81S	0.005 ± 0.004	1	0.4
R81W	0.008 ± 0.005	1	0.7
Y93C	0.08 ± 0.004	11	0.3
Y93H	1.54 ± 0.78	220	0.2
Y93N	6.5 ± 1.25	929	0.5
M28T+Q30H	16 ± 1	2,286	0.7
Q30H+L31V	10 ± 1	1,429	1.1
Q30R+L31V	50 ± 10	7,143	1.1
L31V+Y93H	272 ± 115	38,857	0.5
L31V+Y93N	375 ± 145	53,571	0.5
K24T+M28T+Q30R	49	7,000	1.2
K24Q+M28T+L31 M	0.06	9	0.4
K24 M+Q30R+R81 M	0.48 ± 0.01	69	1.0
M28T+Q30H+L31V	392 ± 34	56,000	0.2
M28T+Q30R+L31V	624 ± 97	89,143	0.7
M28V+Q30H+L31V	17 ± 5	2,429	0.8
M28T+Q30R+L31V+Y93H	5,000	714,286	0.2

^aAverage ± standard deviation; n ≥ 3.

^bChange in potency relative to the WT GT1a(H77) control.

^cFitness range: ≤0.02, unfit; 0.03 to 0.5, moderately fit; >0.5, fit.

^dNT, not tested.