TABLE 4.

Effective inhibitory concentrations of elbasvir against variant replicons^a

Replicon	EC50		EC90
	Mean ± SD (nM)	Fold shiftb	Mean ± SD (nM)	Fold shiftb
1a_H77 (WT)	0.007 ± 0.004		0.017 ± 0.009
1a_M28T	0.108 ± 0.035	15	0.378 ± 0.180	22
1a_M28V	0.009 ± 0.006	1	0.016 ± 0.012	1
1a_M28A	0.427 ± 0.220	61	1.527 ± 0.688	91
1a_Q30Dc	3.7 ± 1.7	925	8.6 ± 3.5	1,433
1a_Q30H	0.045 ± 0.033	6	0.108 ± 0.067	6
1a_Q30R	0.114 ± 0.087	16	0.407 ± 0.212	24
1a_L31V	0.431 ± 0.130	61	2.143 ± 0.737	127
1a_L31M	0.070 ± 0.031	10	0.245 ± 0.162	15
1a_L31F	0.673 ± 0.384	96	2.203 ± 1.605	131
1a_H58D	0.041 ± 0.017	6	0.168 ± 0.066	10
1a_A92P	0.007 ± 0.003	1	0.017 ± 0.005	1
1a_Y93H	1.543 ± 0.782	220	5.930 ± 2.900	351
1a_Y93N	6.552 ± 1.253	929	22.50 ± 8.544	1,333
1a_Y93C	0.078 ± 0.004	11	0.208 ± 0.038	12
1a_Q30D_Y93Nc	86.4 ± 60.1	21,600	257.7 ± 105.7	42,950
1b_con1 (WT)	0.003 ± 0.002		0.006 ± 0.004
1b_L28M	0.006 ± 0.003	2	0.020 ± 0.006	3
1b_L31M	0.003 ± 0.001	1	0.010 ± 0.004	2
1b_L31F	0.046 ± 0.015	15	0.265 ± 0.206	44
1b_L31V	0.013 ± 0.008	4	0.057 ± 0.029	10
1b_Y93H	0.050 ± 0.030	17	0.400 ± 0.200	67
1b_V121I	0.0005 ± 0.0004	0.2	0.0010 ± 0.0007	0.2
GT3_S52 (WT)	0.14 ± 0.09		0.49 ± 0.19
3a_A30K	7.0 ± 1.7	50	20 ± 6.5	41
3a_L31F	20 ± 2	143	45 ± 8	92
3a_E92Kd
3a_Y93H	68 ± 40	485	159 ± 56	324

^aRAV, resistance-associated variant; WT, wild type; EC₅₀, effective concentration to inhibit growth by 50% compared to WT growth; EC₉₀, effective concentration to inhibit growth by 90% compared to WT growth. The genotype 1a results were generated with a transient replicon system (except where indicated), whereas the genotype 1b and genotype 3a data were generated with a stable replicon system.

^bRelative to WT referent.

^cResults were generated with a stable replicon system where genotype 1a_H77 (WT referent) yielded an EC₅₀ of 0.004 nM and an EC₉₀ of 0.006 nM.

^dThe replicon was unable to be generated due to poor fitness.