TABLE 4

Genotypic and phenotypic analysis of GT1a patient viral isolatesa

Dose (mg)GT or patientNadir (h)NS5A RAM(s) at baseline, first 100 aa (%)NS5A RAM(s) at nadir, first 100 aa (%)EDP-239 EC50 (nM)c
BaselineNadirFold change
GT1a (H77)Reference0.006
10530624M28V(2)K24R(2), M/V28T(40)/V(3), Q30H(2)/R(30), L31M(7), F36L(49), H58D(3)/L(2), A92T(1), Y93C(2)/H(8)0.00517.03,400
531024K24R(2), M28V(2)K24R(2), M/V28T(7)/V(5), Q30H(5)/R(45), L31M(8), H58D(2), A92T(3), Y93C(7)/H(12)/N(1)0.0060.2948
531424K24R(4), Q30H(44)Q30H(99)0.0047.41,850
540724M28V(23), H58R(2), Y93F(28)M28V(72), Q30H(4)/R(80), L31M(2), H/R58C(19)/D(8), Y93F(13)0.002>5>2,500
305303b48M28T(17)/V(5), Q30E(2)/H(3)/R(57), H58D(6), Y93C(4)/H(3)0.0100.0434
530748M28T(22), Q30H(7)/R(31), L31V(7), H58D(7), Y93C(7)/H(14)0.0101.7170
531324Q30R(4)M28T(6), Q/R30H(9)/R(87)0.0040.40100
100530148Q30R(94), Y93H(6)0.0075.6800
530848M28V(2)M/V28T(12)/V(10), Q30R(64), Y93C(25)0.0064.7783
531124M28T(9), Q30R(46)0.0110.0091
200530448M28V(29)M/V28A(2)/V(64), Q30E(4)/R(46), Y93C(8)/H(34)/S(3)0.00876.29,525
530524K24N(3)/R(3)/S (1), M28T(90), Q30H(56)/L(2), Q30R(13), F36L(99), H58D(1)/R(1)K24N(2), F36L(99), M28T(94), Q/H30H(78)/E(4)/R(16)776.3222.40.3
530924M28V(43), E62V(25)M28V(63), Q30E(3)/R(58), H58D(7), Y93H(7)/N(10)0.0085.5688
  • a aa, amino acids.

  • b Sequencing of baseline sample failed; 2-h time point used for comparison.

  • c n = 3 independent experiments.