NS3 GT1b
Download full data set for GT1b
Asunaprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (1b_con1) | 0.86 | 1x | likely susceptible | | 2 | 1.2 nM in product label |
| S7A | | | | | | |
| R24W | | | | | | |
| V36A | 1.6 | 2x | likely susceptible | | 2 | |
| V36G | | | Resistance possible | Yes | 2,1,3 | Clinical TE RAV (1,3) |
| V36I | | | | | | |
| V36L | 0.65 | 1x | likely susceptible | | 2 | |
| V36M | 1.9 | 2x | Resistance possible | Yes | 2,3 | Clinical TE RAV (3) |
| V36S | | | | | | |
| A39T | | | | | | |
| Q41L | | | | | | |
| Q41R | | | | | | |
| F43S | 3.2 | 4x | likely susceptible | | 2 | |
| F43I | | | | | | |
| F43L | | | | | | |
| F43V | | | | | | |
| T46S | | | | | | |
| V48I | | | | | | |
| T54A | 0.35 | 0.4x | likely susceptible | | 2 | |
| T54C | | | | | | |
| T54G | | | | | | |
| T54S | 0.7 | 1x | Resistance possible | Yes | 2,3 | Clinical TE RAV (3) |
| V55A | 0.79 | 1x | likely susceptible | | 2,1 | |
| V55I | | | | | | |
| Y56H | | | Resistance possible | Yes | 1 | Clinical TE RAV (1) |
| Y56F | | | | | | |
| Y56L | | | Resistance possible | Yes | 1 | Clinical TE RAV (1) |
| S61L | | | | | | |
| V71I | | | | | | |
| N77S | | | Resistance possible | Yes | 3 | Clinical TE RAV (3) |
| Q80G | | | | | | |
| Q80H | | | | | | |
| Q80I | | | | | | |
| Q80K | 5.6 | February 24, 1900 | resistance likely | Yes | 1,2,3 | Clinical TE RAV (1,3) |
| Q80L | 0.86 | 1x | Resistance possible | Yes | 2,3,8 | Clinical TE RAV (3,4) |
| Q80M | | | | | | |
| Q80R | 3.5 | 4x | Resistance possible | Yes | 2,1,3 | Clinical TE RAV (1,3) |
| Q86R | | | | | | |
| P89L | | | | | | |
| T95S | | | | | | |
| V107I | | | | | | |
| R109K | | | | | | |
| R117C | | | | | | |
| S122A | | | | | | |
| S122D | | | Resistance possible | Yes | 1 | Clinical TE RAV (1) |
| S122G | 0.65 | 1x | Resistance possible | Yes | 1,3,4 | Clinical TE RAV (1,3,4) |
| S122I | | | Resistance possible | Yes | 1,3 | Clinical TE RAV (1,3) |
| S122N | 0.7 | 1x | Resistance possible | Yes | 2,1,3 | Clinical TE RAV (1,3) |
| S122R | | | | | | |
| S122T | 1.2 | 1x | Resistance possible | Yes | 2,1,3 | Clinical TE RAV (1,3) |
| V132I | | | | | | |
| V132L | | | | | | |
| S138T | | | | | | |
| S138P | | | | | | |
| V150A [Conflicting WT, not used in algorithm] | | | | | | |
| R155C | | | | | | |
| R155E | | | | | | |
| R155G | | | Resistance possible | Yes | 1,3 | Clinical TE RAV (1,3) |
| R155I | | | | | | |
| R155K | 23 | 27x | resistance likely | | 2 | |
| R155N | | | | | | |
| R155M | | | | | | |
| R155Q | | | Resistance possible | Yes | 1,3 | Clinical TE RAV (1,3) |
| R155S | | | | | | |
| R155T | | | | | | |
| R155W | | | | | | |
| A156F | | | | | | |
| A156G | | | | | | |
| A156S | 5.9 | 7x | Resistance possible | | 2 | |
| A156T | 5.4 | 6x | Resistance possible | | 2 | |
| A156V | 17 | 20x | resistance likely | | 2 | |
| V158I | | | | | | |
| A166S | | | | | | |
| D168A | 109 | 127x | resistance likely | Yes | 2,1, 3,4 | Clinical TE RAV (3,4) |
| D168C | 56 | 65x | resistance likely | | 2 | |
| D168E | 67 | 78x | resistance likely | Yes | 2,1,3 | Clinical TE RAV (1,3) |
| D168F | | | Resistance possible | Yes | 1,3 | Clinical TE RAV (1,3) |
| D168G | 13 | 16x | resistance likely | Yes | 2,1 | Clinical TE RAV (1) |
| D168H | 85 | 98x | resistance likely | Yes | 1,3 | Clinical TE RAV (1,3) |
| D168I | | | | | | |
| D168K | | | | | | |
| D168L | | | | | | |
| D168N | | | Resistance possible | Yes | 3 | Clinical TE RAV (3) |
| D168Q | | | | | | |
| D168S | | | | | | |
| D168T | | | Resistance possible | Yes | 3 | Clinical TE RAV (3) |
| D168V | 241 | 201-280x | resistance likely | Yes | 2,1,3,4 | Clinical TE RAV (1,3,4) |
| D168Y | 205 | 238x | resistance likely | Yes | 2,1,3 | Clinical TE RAV (1,3) |
| V170A | 1.6 | 2x | Resistance possible | Yes | 2,1 | Clinical TE RAV (1) |
| V170T | | | | | | |
| V170I | 0.72 | 1x | likely susceptible | | 2 | |
| S174F | | | | | | |
| M175L | | | | | | |
| E176G | | | | | | |
| T185S | | | | | | |
| H246Y | | | | | | |
| IT269S | | | | | | |
| S280P | | | | | | |
| I288M | | | | | | |
| N335G | | | | | | |
| T344A | | | | | | |
| E357K | | | | | | |
| T358F | | | | | | |
| G383S | | | | | | |
| S403T | | | | | | |
| I426V | | | | | | |
| T448A | | | | | | |
| M470R | | | | | | |
| I472V | | | | | | |
| V535A | | | | | | |
| P574A | | | | | | |
| P574S | | | | | | |
| V629I | | | | | | |
| V36A+V55A | | | | | | |
| V36A+T54A | | | | | | |
| V36M+R155K | 62 | 72x | resistance likely | | 2,1 | |
| V36M+R155K | | | | | | |
| V36M+A156S | | | | | | |
| Q41R+Q80R | 6.9 | 8x | Resistance possible | | 2 | |
| Q41R+D168V | 202 | 235x | resistance likely | | 2 | |
| F43S+Q80R | | | | | | |
| F43S+D168E | 157 | 183x | resistance likely | | 2 | |
| T54S+V170T | | | | | | |
| T54S+M175L | | | | | | |
| T54S+Y56F | | | | | | |
| T54A+Q80L | | | | | | |
| Y56F+D168Y | | | | | | |
| Y56F+D168E | | | | | | |
| Y56F+Q80L | | | | | | |
| Y56F+Q80R | | | | | | |
| Y56F+S122N | | | | | | |
| Y56F+V170I | | | | | | |
| Y56F+V170T | | | | | | |
| Y56H+D168A | | | | | | |
| Y56H+D168V | | | | | | |
| Y56H+D168V | | | | | | |
| Y56H+D168Y | | | | | | |
| Y65H+D168E | | | | | | |
| Q80H+D168E | | | | | | |
| Q80K+D168Y | | | | | | |
| Q80K+D168V | | | | | | |
| Q80K+R155K | | | | | | |
| Q80L+D168V | | 280x | resistance likely | Yes | 4 | Clincial TE RAV (4) |
| Q80R+D168A | | | | | | |
| Q80R+D168E | | | | | | |
| Q80R+R155K | | | | | | |
| P89L+A156V | | | | | | |
| P89L+A156T | | | | | | |
| S122T+V170I | | | | | | |
| R155K+D168V | | | | | | |
| R155K+V170A | 18 | 21x | resistance likely | | 2 | |
| R155W+A156G | | | | | | |
| R155X+D168X | | | | | | |
| A156G+D168N | | | | | | |
| A156T+D168V | | | | | | |
| A156V+D168V | | | | | | |
| A156V+E176G | | | | | | |
| D168N+V170I | | | | | | |
| T54S+Q80L+V170I | | | | | | |
| Y56F+S122T+V170I | | | | | | |
| Y56F+S122N+V170I | | | | | | |
| R155W+A156G+D168N | | | | | | |
| NS4A V23A | | | | | | |
| 1. Lontok et al. (2015) HEPATOLOGY 62:1623-1632) |
| 2. McPhee et al (2012) AAC-00308 http://aac.asm.org/content/early/2012/04/12/AAC.00308-12.short |
| 3. Sunvepra Canadian Product Monograph 2016 |
| 4. Karino et al. (2013) J Hepatology 58:646-654 |
Boceprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (1b_con1) | | | likely susceptible | | 1 | Clinical TE RAV (1) |
| S7A | | | | | | |
| R24W | | | | | | |
| V36A | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V36G | | | | | | |
| V36I | | | | | | |
| V36L | | | | | | |
| V36M | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V36S | | | | | | |
| A39T | | | | | | |
| Q41L | | | | | | |
| Q41R | | | | | | |
| F43S | | | | | | |
| F43I | | | | | | |
| F43L | | | | | | |
| F43V | | | | | | |
| T46S | | | | | | |
| V48I | | | | | | |
| T54A | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| T54C | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| T54G | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| T54S | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V55A | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V55I | | | | | | |
| Y56H | | | | | | |
| Y56F | | | | | | |
| Y56L | | | | | | |
| S61L | | | | | | |
| V71I | | | | | | |
| N77S | | | | | | |
| Q80G | | | | | | |
| Q80H | | | | | | |
| Q80I | | January 1, 1970 | | | | |
| Q80K | | | | | | |
| Q80L | | | | | | |
| Q80M | | | | | | |
| Q80R | | | | | | |
| Q86R | | | | | | |
| P89L | | | | | | |
| T95S | | | | | | |
| V107I | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| R109K | | | | | | |
| R117C | | | | | | |
| S122A | | | | | | |
| S122D | | | | | | |
| S122G | | | | | | |
| S122I | | | | | | |
| S122N | | | | | | |
| S122R | | | | | | |
| S122T | | | | | | |
| V132I | | | | | | |
| V132L | | | | | | |
| S138T | | | | | | |
| S138P | | | | | | |
| V150A [Conflicting WT, not used in algorithm] | | | | | | |
| R155C | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| R155E | | | | | | |
| R155G | | | | | | |
| R155I | | | | | | |
| R155K | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| R155N | | | | | | |
| R155M | | | | | | |
| R155Q | | | | | | |
| R155S | | | | | | |
| R155T | | | | | | |
| R155W | | | | | | |
| A156F | | | | | | |
| A156G | | | | | | |
| A156S | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| A156T | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| A156V | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V158I | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| A166S | | | | | | |
| D168A | | | | | | |
| D168C | | | | | | |
| D168E | | | | | | |
| D168F | | | | | | |
| D168G | | | | | | |
| D168H | | | | | | |
| D168I | | | | | | |
| D168K | | | | | | |
| D168L | | | | | | |
| D168N | | | | | | |
| D168Q | | | | | | |
| D168S | | | | | | |
| D168T | | | | | | |
| D168V | | | | | | |
| D168Y | | | | | | |
| V170A | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V170T | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V170I | | | | | | |
| S174F | | | | | | |
| M175L | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| E176G | | | | | | |
| T185S | | | | | | |
| H246Y | | | | | | |
| IT269S | | | | | | |
| S280P | | | | | | |
| I288M | | | | | | |
| N335G | | | | | | |
| T344A | | | | | | |
| E357K | | | | | | |
| T358F | | | | | | |
| G383S | | | | | | |
| S403T | | | | | | |
| I426V | | | | | | |
| T448A | | | | | | |
| M470R | | | | | | |
| I472V | | | | | | |
| V535A | | | | | | |
| P574A | | | | | | |
| P574S | | | | | | |
| V629I | | | | | | |
| V36A+V55A | | | | | | |
| V36A+T54A | | | | | | |
| V36M+R155K | | | | | | |
| V36M+R155K | | | | | | |
| V36M+A156S | | | | | | |
| Q41R+Q80R | | | | | | |
| Q41R+D168V | | | | | | |
| F43S+Q80R | | | | | | |
| F43S+D168E | | | | | | |
| T54S+V170T | | | | | | |
| T54S+M175L | | | | | | |
| T54S+Y56F | | | | | | |
| T54A+Q80L | | | | | | |
| Y56F+D168Y | | | | | | |
| Y56F+D168E | | | | | | |
| Y56F+Q80L | | | | | | |
| Y56F+Q80R | | | | | | |
| Y56F+S122N | | | | | | |
| Y56F+V170I | | | | | | |
| Y56F+V170T | | | | | | |
| Y56H+D168A | | | | | | |
| Y56H+D168V | | | | | | |
| Y56H+D168V | | | | | | |
| Y56H+D168Y | | | | | | |
| Y65H+D168E | | | | | | |
| Q80H+D168E | | | | | | |
| Q80K+D168Y | | | | | | |
| Q80K+D168V | | | | | | |
| Q80K+R155K | | | | | | |
| Q80L+D168V | | | | | | |
| Q80R+D168A | | | | | | |
| Q80R+D168E | | | | | | |
| Q80R+R155K | | | | | | |
| P89L+A156V | | | | | | |
| P89L+A156T | | | | | | |
| S122T+V170I | | | | | | |
| R155K+D168V | | | | | | |
| R155K+V170A | | | | | | |
| R155W+A156G | | | | | | |
| R155X+D168X | | | | | | |
| A156G+D168N | | | | | | |
| A156T+D168V | | | | | | |
| A156V+D168V | | | | | | |
| A156V+E176G | | | | | | |
| D168N+V170I | | | | | | |
| T54S+Q80L+V170I | | | | | | |
| Y56F+S122T+V170I | | | | | | |
| Y56F+S122N+V170I | | | | | | |
| R155W+A156G+D168N | | | | | | |
| NS4A V23A | | | | | | |
| 1. Lontok et al. (2015) HEPATOLOGY 62:1623-1632) |
Glecaprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Replicative Fitness (3) | Reference | Comments |
| WT (1b_con1) | 0.47 | 1x | likely susceptible | | 100 | 2,1 | |
| S7A | | | | | | | |
| R24W | | | | | | | |
| V36A | | | | | | | |
| V36G | | | | | | | |
| V36I | | | | | | | |
| V36L | | | | | | | |
| V36M | | | | | | | |
| V36S | | | | | | | |
| A39T | | | | | | | |
| Q41L | | | | | | | |
| Q41R | | | | | | | |
| F43S | | | | | | | |
| F43I | | | | | | | |
| F43L | | | | | | | |
| F43V | | | | | | | |
| T46S | | | | | | | |
| V48I | | | | | | | |
| T54A | 0.45 | 1x | likely susceptible | | 59 | 3 | |
| T54C | | | | | | | |
| T54G | | | | | | | |
| T54S | unfit | | | | <0.5 | 3 | |
| V55A | 0.21 | 0.4x | likely susceptible | | 14 | 3 | |
| V55I | | | | | | | |
| Y56H | unfit | | | | <0.5 | 3 | |
| Y56F | unfit | | Resistance possible | Yes | 1.1 | 2,3 | Clinical VF RAV (2) |
| Y56L | | | | | | | |
| S61L | | | | | | | |
| V71I | | | | | | | |
| N77S | | | | | | | |
| Q80G | | | | | | | |
| Q80H | | | | | | | |
| Q80I | | | | | | | |
| Q80K | 0.37 | 0.8x | likely susceptible | | 162 | 3 | |
| Q80L | 0.3 | 0.6x | likely susceptible | | 123 | 3 | |
| Q80M | | | | | | | |
| Q80R | | | | | | | |
| Q86R | | | | | | | |
| P89L | 1.1 | 2.4x | likely susceptible | | 172 | 3 | |
| T95S | | | | | | | |
| V107I | | | | | | | |
| R109K | | | | | | | |
| R117C | | | | | | | |
| S122A | | | | | | | |
| S122D | | | | | | | |
| S122G | | | | | | | |
| S122I | | | | | | | |
| S122N | | | | | | | |
| S122R | | | | | | | |
| S122T | | | | | | | |
| V132I | | | | | | | |
| V132L | | | | | | | |
| S138T | | | | | | | |
| S138P | | | | | | | |
| V150A [Conflicting WT, not used in algorithm] | | | | | | | |
| R155C | | | | | | | |
| R155E | | | | | | | |
| R155G | | | | | | | |
| R155I | | | | | | | |
| R155K | 0.27 | 0.6x | likely susceptible | | 73 | 3 | |
| R155N | | | | | | | |
| R155M | | | | | | | |
| R155Q | unfit | | likely susceptible | | <0.5 | 3 | |
| R155S | | | | | | | |
| R155T | | | | | | | |
| R155W | | | | | | | |
| A156F | | | | | | | |
| A156G | | | | | | | |
| A156S | 0.2 | 0.4x | likely susceptible | | 61 | 3 | |
| A156T | 301 | 640x | resistance likely | | 19 | 2,3 | |
| A156V | 840 | 1800x | resistance likely | | 9.2 | 2,3 | |
| V158I | | | | | | | |
| A166S | | | | | | | |
| D168A | 0.69 | 1.5x | likely susceptible | | 69 | 3 | |
| D168C | | | | | | | |
| D168E | 0.4 | 0.9x | likely susceptible | | 80 | 3 | |
| D168F | 2.5 | 5.3x | Resistance possible | | 105 | 3 | |
| D168G | | | | | | | |
| D168H | 0.68 | 1.4x | likely susceptible | | 108 | 3 | |
| D168I | | | | | | | |
| D168K | 5.3 | 11x | resistance likely | | 50 | 3 | |
| D168L | | | | | | | |
| D168N | | | | | | | |
| D168Q | | | | | | | |
| D168S | | | | | | | |
| D168T | 1.3 | 2.8x | Resistance possible | | 129 | 3 | |
| D168V | 1.5 | 3.2x | Resistance possible | | 157 | 3 | |
| D168Y | 0.99 | 2.1x | likely susceptible | | 70 | 3 | |
| V170A | 0.49 | 1.1x | likely susceptible | | 64 | 3 | |
| V170T | | | | | | | |
| V170I | | | | | | | |
| S174F | | | | | | | |
| M175L | | | | | | | |
| E176G | 1.3 | 2.7x | Resistance possible | | 6 | 3 | |
| T185S | | | | | | | |
| H246Y | | | | | | | |
| IT269S | | | | | | | |
| S280P | | | | | | | |
| I288M | | | | | | | |
| N335G | | | | | | | |
| T344A | | | | | | | |
| E357K | | | | | | | |
| T358F | | | | | | | |
| G383S | | | | | | | |
| S403T | | | | | | | |
| I426V | | | | | | | |
| T448A | | | | | | | |
| M470R | | | | | | | |
| I472V | | | | | | | |
| V535A | | | | | | | |
| P574A | | | | | | | |
| P574S | | | | | | | |
| V629I | | | | | | | |
| V36A+V55A | | | | | | | |
| V36A+T54A | | | | | | | |
| V36M+R155K | | | | | | | |
| V36M+R155K | | | | | | | |
| V36M+A156S | | | | | | | |
| Q41R+Q80R | | | | | | | |
| Q41R+D168V | | | | | | | |
| F43S+Q80R | | | | | | | |
| F43S+D168E | | | | | | | |
| T54S+V170T | | | | | | | |
| T54S+M175L | | | | | | | |
| T54S+Y56F | | | | | | | |
| T54A+Q80L | | | | | | | |
| Y56F+D168Y | 35.6 | 76x | resistance likely | | | 3 | |
| Y56F+D168E | unfit | | | | | 3 | |
| Y56F+Q80L | 0.28 | 0.6x | likely susceptible | | 96 | 3 | |
| Y56F+Q80R | | | | | | | |
| Y56F+S122N | | | | | | | |
| Y56F+V170I | | | | | | | |
| Y56F+V170T | | | | | | | |
| Y56H+D168A | 8 | 17x | resistance likely | | 6 | 3 | |
| Y56H+D168V | 7.2 | 15x | resistance likely | | 22 | 3 | |
| Y56H+D168V | 7.2 | 15x | resistance likely | | 22 | 3 | |
| Y56H+D168Y | 35.6 | 76x | resistance likely | | 8 | 3 | |
| Y65H+D168E | unfit | | | | <0.5 | 3 | |
| Q80H+D168E | | | | | | | |
| Q80K+D168Y | 35.6 | 76x | resistance likely | | 8 | 3 | |
| Q80K+D168V | 0.79 | 1.7x | likely susceptible | | 132 | 3 | |
| Q80K+R155K | | | | | | | |
| Q80L+D168V | | | | | | | |
| Q80R+D168A | | | | | | | |
| Q80R+D168E | | | | | | | |
| Q80R+R155K | | | | | | | |
| P89L+A156V | 2100 | 4500x | resistance likely | | 119 | 2,3 | |
| P89L+A156T | 787 | 1674x | resistance likely | | 113 | 3 | |
| S122T+V170I | | | | | | | |
| R155K+D168V | | | | | | | |
| R155K+V170A | | | | | | | |
| R155W+A156G | | | | | | | |
| R155X+D168X | | | | | | | |
| A156G+D168N | | | | | | | |
| A156T+D168V | 643 | 1368x | resistance likely | | 21 | 3 | |
| A156V+D168V | 2465 | 5244 | resistance likely | | 17 | 3,2 | |
| A156V+E176G | 1113 | 2368x | resistance likely | | 43 | 3 | |
| D168N+V170I | | | | | | | |
| T54S+Q80L+V170I | | | | | | | |
| Y56F+S122T+V170I | | | | | | | |
| Y56F+S122N+V170I | | | | | | | |
| R155W+A156G+D168N | | | | | | | |
| NS4A V23A | | | | | | | |
| 1. Poordad F, et al. 2016. In vitro 1: 3 |
| 2. Ng et al. [Abstract 636]. -CROI. Boston, 2014 http://www.croiconference.org/sites/all/abstracts/636.pdf |
| 3. FDA Microbiology Review https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209394Orig1s000MicroR.pdf |
Grazoprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments | SVR with BL RAS in a 12-wk Rx |
| WT (1b_con1) | 0.5 | 1x | likely susceptible | | 1,7 | 0.5-0..94; clinical isolate=0.3 (0.05-3.8) | 0.95 |
| S7A | | | | | | | |
| R24W | | | | | | | |
| V36A | 1 | 2x | likely susceptible | | 7,2 | | 100% (7) |
| V36G | | | | | | | |
| V36I | 0.2 | 0.4x | likely susceptible | | 7 | | |
| V36L | 0.5 | 1x | likely susceptible | | 2,6,7 | | |
| V36M | 0.9 | 2x | likely susceptible | | 2,4,6,7,8 | | 100% (7) |
| V36S | | | | | | | |
| A39T | | | | | | | |
| Q41L | 0.1 | 0.2x | likely susceptible | | 7 | | |
| Q41R | 1.1 | 2.2x | likely susceptible | | 7 | | |
| F43S | 1.3 | 2.6 | likely susceptible | | 2,3 | | |
| F43I | | | | | | | |
| F43L | | | | | | | |
| F43V | | | | | | | |
| T46S | | | | | | | |
| V48I | | | | | | | |
| T54A | 0.6 | 1.2x | likely susceptible | | 7,8 | | 100% (7) |
| T54C | 0.8 | 1.6x | likely susceptible | | 7 | | |
| T54G | 0.8 | 1.7x | likely susceptible | | 7 | | |
| T54S | 0.6 | 1.2x | Resistance possible | Yes | 6,7 | Clinical VF RAS (7) | 50% (7) |
| V55A | 0.7 | 1.4x | likely susceptible | | 2,6 | | |
| V55I | 0.7 | 1.4x | likely susceptible | | 6 | | |
| Y56H | 6.3 | 13x | resistance likely | Yes | 1,4,6,7 | Clinical TE RAV (1,6) | |
| Y56F | 0.7 | 1.7x | Resistance possible | Yes | 3,1,6,7 | Clinical TE RAV (3,1,7) | |
| Y56L | | | | | | | |
| S61L | | | | | | | |
| V71I | | | | | | | |
| N77S | | | | | | | |
| Q80G | | | | | | | |
| Q80H | | | | | | | |
| Q80I | | | | | | | |
| Q80K | | | | | | | |
| Q80L | 1.1 | 2.1x | Resistance possible | Yes | 7 | Clinical VF RAV (7) | |
| Q80M | | | | | | | |
| Q80R | 1 | 2x | likely susceptible | | 2,7 | | |
| Q86R | | 0.2x | likely susceptible | | 7 | | |
| P89L | | | | | | | |
| T95S | | | | | | | |
| V107I | 0.5 | 1x | Resistance possible | Yes | 1,4,3,7 | Clinical TE RAV (3,1,7) | |
| R109K | | | | | | | |
| R117C | | | | | | | |
| S122A | 0.4 | 0.8x | likely susceptible | | 7 | | |
| S122D | | | | | | | |
| S122G | 0.3 | 0.5x | likely susceptible | | 7 | | |
| S122I | | | | | | | |
| S122N | | | Resistance possible | Yes | 7 | Clincial VF RAV (7) | |
| S122R | 0.5 | 1x | Resistance possible | Yes | 6,4,7 | Clincial VF RAV (7) | |
| S122T | 0.6 | 2x | Resistance possible | Yes | 7 | Clincial VF RAV (7) | |
| V132I | 0.5 | 1x | Resistance possible | Yes | 6,7 | Clincial VF RAV (7) | |
| V132L | | | Resistance possible | Yes | 7 | Clincial VF RAV (7) | |
| S138T | | | | | | | |
| S138P | | | | | | | |
| V150A [Conflicting WT, not used in algorithm] | | | | | | | |
| R155C | | | | | | | |
| R155E | 1.4 | 2.7x | likely susceptible | | 7 | | |
| R155G | 14 | 28x | resistance likely | | 1,2,7 | | |
| R155I | | | | | | | |
| R155K | 1.1 | 2.2x | likely susceptible | | 2,7 | | |
| R155N | 0.9 | 1.9x | likely susceptible | | 7 | | |
| R155M | | | | | | | |
| R155Q | 1.2 | 2.4x | Resistance possible | Yes | 7 | Clincial VF RAV (7) | |
| R155S | 1.7 | 3.4x | likely susceptible | | 7 | | |
| R155T | 6.5 | 13x | resistance likely | | 1,7 | | |
| R155W | 13.5 | 27x | resistance likely | Yes | 1,6,7 | Clinical TE RAV (6) | |
| A156F | | | | | | | |
| A156G | 0.7 | 1x | likely susceptible | | 4,6,7 | | |
| A156S | 1.1 | 2.1x | likely susceptible | | 7 | | |
| A156T | 140 | 280x-333x | resistance likely | Yes | 1,4,3,2,6,7,8 | Clinical TE RAV (3,1,6,7) | |
| A156V | 187.5 | 375x | resistance likely | | 1,4,3,7 | | |
| V158I | | | | | | | |
| A166S | | | | | | | |
| D168A | 7 | 14x-51x | resistance likely | Yes | 1,2,4,3,6,7,8 | Clinical TE RAV (7) | |
| D168C | | | | | | | |
| D168E | 1.6 | 16x | resistance likely | Yes | 2,6,7,8 | Clinical TE RAV (6,7) | 100% (7) |
| D168F | 38 | 76x | resistance likely | | 1,7 | | |
| D168G | 5.5 | 11x | resistance likely | | 1,2,3,7 | | |
| D168H | 25.5 | 51x | resistance likely | | 1,7 | | |
| D168I | 6.5 | 13x | resistance likely | | 1,7 | | |
| D168K | 60.5 | 121x | resistance likely | | 1,2,7 | | |
| D168L | 7.5 | 15x | resistance likely | | 1,7 | | |
| D168N | 0.4 | 1x | Resistance possible | Yes | 4,6,7 | Clinical TE RAV (6,7) | 100% (7) |
| D168Q | | | | | | | |
| D168S | 2 | 4.1x | likely susceptible | | 7 | | |
| D168T | 13 | 26x | resistance likely | | 1,6,7 | | |
| D168V | 7 | 14x-22x | resistance likely | Yes | 1,4,3,6,7,8 | Clinical TE RAV (7) | 100% (7) |
| D168Y | 4 | 8x | Resistance possible | | 1,4,6,7 | | |
| V170A | 0.7 | 1.4x | likely susceptible | | 7 | | |
| V170T | 0.5 | 1x | likely susceptible | | 2,7 | | |
| V170I | 0.4 | 1x | Resistance possible | Yes | 6,7 | Clinical VF RAS (6) | |
| S174F | | | | | | | |
| M175L | | | | | | | |
| E176G | | | | | | | |
| T185S | | | Resistance possible | Yes | 7 | Clinical TE RAV (7) | |
| H246Y | | | | | | | |
| IT269S | | | | | | | |
| S280P | | | | | | | |
| I288M | | | | | | | |
| N335G | | | | | | | |
| T344A | | | | | | | |
| E357K | | | Resistance possible | Yes | 7 | Clinical TE RAV (7) | |
| T358F | | | | | | | |
| G383S | | | | | | | |
| S403T | | | | | | | |
| I426V | | | | | | | |
| T448A | | | | | | | |
| M470R | | | | | | | |
| I472V | | | | | | | |
| V535A | | | | | | | |
| P574A | | | | | | | |
| P574S | | | | | | | |
| V629I | | | | | | | |
| V36A+V55A | | | | | | | |
| V36A+T54A | | | | | | | |
| V36M+R155K | | | | | | | |
| V36M+R155K | | | | | | | |
| V36M+A156S | | | | | | | |
| Q41R+Q80R | | | | | | | |
| Q41R+D168V | | | | | | | |
| F43S+Q80R | | | | | | | |
| F43S+D168E | | | | | | | |
| T54S+V170T | | | | | | | |
| T54S+M175L | | | | | | | |
| T54S+Y56F | | | | | | | |
| T54A+Q80L | | | | | | | |
| Y56F+D168Y | | | | | | | |
| Y56F+D168E | | | | | | | |
| Y56F+Q80L | | | | | | | |
| Y56F+Q80R | | | | | | | |
| Y56F+S122N | | | | | | | |
| Y56F+V170I | | | | | | | |
| Y56F+V170T | | | | | | | |
| Y56H+D168A | 303 | 606x | resistance likely | | 4,7 | | |
| Y56H+D168V | | | | | | | |
| Y56H+D168V | | | | | | | |
| Y56H+D168Y | | | | | | | |
| Y65H+D168E | | | | | | | |
| Q80H+D168E | | | | | | | |
| Q80K+D168Y | | | | | | | |
| Q80K+D168V | | | | | | | |
| Q80K+R155K | | | | | | | |
| Q80L+D168V | | | | | | | |
| Q80R+D168A | | | | | | | |
| Q80R+D168E | 17.1 | 34.3x | resistance likely | | 7 | | |
| Q80R+R155K | | | | | | | |
| P89L+A156V | | | | | | | |
| P89L+A156T | | | | | | | |
| S122T+V170I | | | | | | | |
| R155K+D168V | | | | | | | |
| R155K+V170A | | | | | | | |
| R155W+A156G | 1540 | 3160x | resistance likely | | 6,7 | | |
| R155X+D168X | | | | | | | |
| A156G+D168N | 9 | 18.2 | resistance likely | | 7 | | |
| A156T+D168V | | | | | | | |
| A156V+D168V | | | | | | | |
| A156V+E176G | | | | | | | |
| D168N+V170I | | | | | | | |
| T54S+Q80L+V170I | 0.5 | 0.9x | likely susceptible | | 7 | | |
| Y56F+S122T+V170I | | | | | | | |
| Y56F+S122N+V170I | | | | | | | |
| R155W+A156G+D168N | 278 | 556x | resistance likely | | 6,7 | | |
| NS4A V23A | | | | | | | |
| 1. Zapatier Canadian Product Label |
| 2. Howe et al. (2014) CID 59(12): 1657-1665. |
| 3. Zepatier US Product Label |
| 4. Black S, et al. 2015. Journal of Hepatology 62: S677-S8. http://www.natap.org/2015/EASL/EASL_107.htm |
| 5. Lahser FC, et al. 2016. Antimicrobial agents and chemotherapy 60: 2954-64. AAC doi: 10.1128/AAC.00051-16 |
| 6. Bonsall et al. (2018) Infection and Drug Resistance (in press) |
| 7. FDA Microbiology/Virology Reviews Zepatier_208261Orit1s000 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208261Orig1s000MicroR.pdf |
| 8. FDA Vosevi Microbiology Reviews 209195Orig1s000MicroR |
Paritaprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (1b_con1) | 0.21 | 1x | likely susceptible | | 2 | |
| S7A | | | | | | |
| R24W | | | | | | |
| V36A | | | | | | |
| V36G | | | | | | |
| V36I | | | | | | |
| V36L | | | | | | |
| V36M | | | | | | |
| V36S | | | | | | |
| A39T | | | | | | |
| Q41L | | | | | | |
| Q41R | | | | | | |
| F43S | | | | | | |
| F43I | | | | | | |
| F43L | | | | | | |
| F43V | | | | | | |
| T46S | | | | | | |
| V48I | | | | | | |
| T54A | 0.09 | 1x | likely susceptible | | 1,8 | |
| T54C | | | | | | |
| T54G | | | | | | |
| T54S | | | | | | |
| V55A | 0.07 | 1x | likely susceptible | | 8,1 | |
| V55I | | | | | | |
| Y56H | unfit | | Resistance possible | Yes | 4,6,3,2,7,8 | Clinical TE RAV (6,7,2,8); clinical VF RAV (4 |
| Y56F | | | Resistance possible | Yes | 8 | Clinical VF RAS (8) |
| Y56L | | | | | | |
| S61L | | | | | | |
| V71I | | | | | | |
| N77S | | | | | | |
| Q80G | | | | | | |
| Q80H | | | | | | |
| Q80I | | | | | | |
| Q80K | | | | | | |
| Q80L | | | | | | |
| Q80M | | | | | | |
| Q80R | | | | | | |
| Q86R | | | | | | |
| P89L | | | | | | |
| T95S | | | | | | |
| V107I | | | | | | |
| R109K | | | | | | |
| R117C | | | | | | |
| S122A | | | | | | |
| S122D | | | | | | |
| S122G | | | | | | |
| S122I | | | | | | |
| S122N | | | | | | |
| S122R | | | | | | |
| S122T | | | | | | |
| V132I | | | | | | |
| V132L | | | | | | |
| S138T | | | | | | |
| S138P | | | | | | |
| V150A [Conflicting WT, not used in algorithm] | | | | | | |
| R155C | | | | | | |
| R155E | | | | | | |
| R155G | | | | | | |
| R155I | | | | | | |
| R155K | 4.4 | 40x | resistance likely | | 8,1,3 | |
| R155N | | | | | | |
| R155M | | | | | | |
| R155Q | unfit | unfit | | | 1,7,8 | replicon RAV (7), not found in pt |
| R155S | | | | | | |
| R155T | | | | | | |
| R155W | | | | | | |
| A156F | | | | | | |
| A156G | | | | | | |
| A156S | 0.06 | 0.5x | likely susceptible | | 1,8 | |
| A156T | 0.81 | 7x | Resistance possible | | 1, 2,3,8 | |
| A156V | | 21x | resistance likely | | 3 | |
| V158I | | | | | | |
| A166S | | | | | | |
| D168A | 3 | 27x | resistance likely | Yes | 1,4,2,6,3,8 | clinical VF RAV (2,4,6) |
| D168C | | | | | | |
| D168E | 0.48 | 4x | likely susceptible | | 8,1, 6 | |
| D168F | | 173x | resistance likely | Yes | 2,3 | clinical TE RAV (2) |
| D168G | | | | | | |
| D168H | 8.3 | 76x | resistance likely | Yes | 8,1,2,3 | Clinical TE RAV (2); replicon RAV (7) |
| D168I | | | Resistance possible | Yes | 2 | clinical TE RAV (2) |
| D168K | 96 | 873x | resistance likely | Yes | 8,4,2,3 | clinical VF RAV (4) |
| D168L | | | Resistance possible | Yes | 2 | clinical TE RAV (2) |
| D168N | | | Resistance possible | Yes | 2 | clinical TE RAV (2) |
| D168Q | | | | | | |
| D168S | | | | | | |
| D168T | 5.4 | 49x | resistance likely | Yes | 1,3,8 | clinical TE RAV (2) |
| D168V | 17 | 159x | resistance likely | Yes | 1, 5, 4,2,6,7,3,8 | Clinical TE RAV (2,6,7,8); clinical VF RAV (4,5) |
| D168Y | 37 | 337x | resistance likely | Yes | 1,3,8 | clinical TE RAV (2) |
| V170A | 0.09 | 1x | likely susceptible | | 1,8 | |
| V170T | | | | | | |
| V170I | | | | | | |
| S174F | | | | | | |
| M175L | | | | | | |
| E176G | | | | | | |
| T185S | | | | | | |
| H246Y | | | | | | |
| IT269S | | | | | | |
| S280P | | | | | | |
| I288M | | | | | | |
| N335G | | | | | | |
| T344A | | | | | | |
| E357K | | | Resistance possible | Yes | 2,8 | clincial TE RAV (8), helicase domain (2) |
| T358F | | | | | | |
| G383S | | | | | | |
| S403T | | | | | | |
| I426V | | | | | | |
| T448A | | | | | | |
| M470R | | | | | | |
| I472V | | | | | | |
| V535A | | | | | | |
| P574A | | | | | | |
| P574S | | | | | | |
| V629I | | | | | | |
| V36A+V55A | | | | | | |
| V36A+T54A | | unfit | | | | |
| V36M+R155K | | | | | | |
| V36M+R155K | | | | | | |
| V36M+A156S | | | | | | |
| Q41R+Q80R | | | | | | |
| Q41R+D168V | | | | | | |
| F43S+Q80R | | | | | | |
| F43S+D168E | | | | | | |
| T54S+V170T | | | | | | |
| T54S+M175L | | | | | | |
| T54S+Y56F | | | | | | |
| T54A+Q80L | | | | | | |
| Y56F+D168Y | | | | | | |
| Y56F+D168E | | | | | | |
| Y56F+Q80L | | | | | | |
| Y56F+Q80R | | | | | | |
| Y56F+S122N | | | | | | |
| Y56F+V170I | | | | | | |
| Y56F+V170T | | | | | | |
| Y56H+D168A | 77 | 700 | resistance likely | | 6,2,8 | +15-26 FS vs single D168 subst (2,6) |
| Y56H+D168V | | | | | | |
| Y56H+D168V | 272 | 2472x | resistance likely | | 4,6,7,8 | +15-26 FS vs single D168 subst (2,6) |
| Y56H+D168Y | 453 | 4118x | resistance likely | | 8 | |
| Y65H+D168E | | | | | | |
| Q80H+D168E | | | | | | |
| Q80K+D168Y | | | | | | |
| Q80K+D168V | | | | | | |
| Q80K+R155K | | | | | | |
| Q80L+D168V | | | | | | |
| Q80R+D168A | | | | | | |
| Q80R+D168E | | | | | | |
| Q80R+R155K | | | | | | |
| P89L+A156V | | | | | | |
| P89L+A156T | | | | | | |
| S122T+V170I | | | | | | |
| R155K+D168V | | | | | | |
| R155K+V170A | | | | | | |
| R155W+A156G | | | | | | |
| R155X+D168X | | | | | | |
| A156G+D168N | | | | | | |
| A156T+D168V | | | | | | |
| A156V+D168V | | | | | | |
| A156V+E176G | | | | | | |
| D168N+V170I | | | | | | |
| T54S+Q80L+V170I | | | | | | |
| Y56F+S122T+V170I | | | | | | |
| Y56F+S122N+V170I | | | | | | |
| R155W+A156G+D168N | | | | | | |
| NS4A V23A | | | Resistance possible | | 2,8 | clincial TE RAV(8), helicase domain (2) |
| 1. Pilot-Matias et al. (2015) AAC 59(2):988-997 |
| 2. Viekira Pak US Product Label jan 28, 2016 |
| 3. Sulkowski et al (2016) CROI poster 16LB-3113 |
| 4. 3. Lontok et al. (2015) HEPATOLOGY 62:1623-1632 |
| 5. Poordad et al (2014) NEJM 370 (21):1973 – 1982 |
| 6. Krishnan P, et al. 2015. Antimicrobial agents and chemotherapy: AAC-02606 doi:10.1128/AAC.02606-15 |
| 7. Holkira Canadian Product Monograph Oct 14, 2015 |
| 8. FDA Microbiology/Virology Viekira Pak Review 206619Orig1s000 |
Simeprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | VF in SMV+P/R (#pts) | Comments |
| WT (1b_con1) | 11 | 1x | likely susceptible | | 1 | | |
| S7A | | | | | | 1 | |
| R24W | | | | | | 1 | |
| V36A | 34 | 2.8 | likely susceptible | | 1,4,6 | | |
| V36G | | 3.6x | likely susceptible | | 6 | | |
| V36I | 18 | 1.7x | likely susceptible | | | | |
| V36L | 18 | 1.7x | likely susceptible | | 1 | | |
| V36M | 20 | 2x | likely susceptible | | 1,4,7 | | |
| V36S | | | | | | | |
| A39T | | | Resistance possible | Yes | 6 | 13 | Clinical TE RAS (6) |
| Q41L | | | | | | | |
| Q41R | | 1.8x | likely susceptible | | 6 | | |
| F43S | 83 | 12x | resistance likely | | 1,4 | | |
| F43I | 562 | 89x | resistance likely | | 1,4 | | |
| F43L | | 4x | likely susceptible | | 4 | | |
| F43V | 626 | 99x | resistance likely | | 1,3 | | |
| T46S | | | Resistance possible | Yes | 6 | 2 | |
| V48I | | | Resistance possible | Yes | 4 | 2 | Clinical TE RAS, 50% NGS (4) |
| T54A | 5.9 | 0.6x | likely susceptible | | 1,7 | | |
| T54C | | | | | | | |
| T54G | | | | | | | |
| T54S | 5.4 | 1.2x | likely susceptible | | 1 | | |
| V55A | | | | | | | |
| V55I | | | | | | | |
| Y56H | | | | | | | |
| Y56F | | | | | | | |
| Y56L | | | | | | | |
| S61L | | | Resistance possible | Yes | 6 | 2 | Clinical TE RAS (6) |
| V71I | | | | | 6 | 2 | Clincial VF RAS, >10% NGS (6) |
| N77S | | | | | | | |
| Q80G | 22 | 1.8x | likely susceptible | | 1,4 | | |
| Q80H | 41 | 8x | Resistance possible | | 1,4 | | 4 - 8x FS |
| Q80I | | | | | 2 | | no specific Clincial RAS indicated (2) |
| Q80K | 62 | 7.7x | resistance likely | Yes | 3,4,6 | 14 | Clinical TE RAV (2,3,6) |
| Q80L | 12 | 2.1x | likely susceptible | | 1 | | |
| Q80M | | | | | 2 | | no specific Clincial RAS indicated (2) |
| Q80R | 49 | 6.9x | resistance likely | Yes | 1,3,4,6 | 10 | Clinical TE RAV (2,3,6) |
| Q86R | | | Resistance possible | Yes | 6 | 16 | Clincial TE RAS (6) |
| P89L | | | | | | | |
| T95S | | | | | | 1 | |
| V107I | | | | | | | |
| R109K | 11 | 0.7x | likely susceptible | | 1 | | |
| R117C | | | Resistance possible | Yes | 6 | 1 | Cliincal TE RAS, 49% NGS (6) |
| S122A | | | Resistance possible | Yes | 3 | <8 | Clinical SMV+SOF TE RAV (2,3) |
| S122D | | | | | | | |
| S122G | | | Resistance possible | Yes | 6 | <8 | Clincal SMV+SOF TE VF RAS (6) |
| S122I | | | Resistance possible | Yes | 2,3 | | Clinical SMV+SOF TE RAV (2,3) |
| S122N | | | | | | | |
| S122R | | 20x | resistance likely | | 4 | <8 | |
| S122T | | | Resistance possible | Yes | 3 | <8 | Clinical SMV+SOF TE RAV (2,3) |
| V132I | | | | | | | |
| V132L | | | | | | | |
| S138T | 77 | 4.4x | likely susceptible | | 1 | | |
| S138P | | | | | | 1 | clincal SMV+PR RAS |
| V150A [Conflicting WT, not used in algorithm] | | | Resistance possible | Yes | 6 | 2 | Clincial VF RAS, 50% NGS |
| R155C | | | | | 2 | | no specific Clincial RAS indicated (2) |
| R155E | | | | | | | |
| R155G | 350 | 20x | resistance likely | Yes | 1 | | Clinical TE RAV (3) |
| R155I | 6.6 | 0.8x | likely susceptible | | 1 | | |
| R155K | 260 | 18-30x | resistance likely | | 1,6 | | |
| R155N | | | | | | | |
| R155M | 3.5 | 0.4x | likely susceptible | | 1 | | |
| R155Q | 21 | April 29, 1900 | resistance likely | Yes | 1,4,6 | 4 | Clinical TE RAV (2,3,6). '9-28x FS |
| R155S | | January 1, 1970 | | | | | |
| R155T | 314 | 24x | resistance likely | | 1 | | |
| R155W | | 100x | resistance likely | | 4 | | |
| A156F | | | | | | | |
| A156G | 206 | 16x | resistance likely | | 1,6 | | 9-16x FS |
| A156S | 3 | 0.3x | Resistance possible | Yes | 4 | 1 | Clinical VF RAV (4) |
| A156T | 377 | 44x | resistance likely | Yes | 1,7,6 | | Clinical VF RAV (4) |
| A156V | 2149 | 177x | resistance likely | Yes | 1,7,6 | 1 | Clinical TE RAV (2) |
| V158I | | | | | | | |
| A166S | | | | | | | |
| D168A | 6356 | 475x-594x | resistance likely | Yes | 1,6,7 | 7 | Clinical VF RAV (4,6) |
| D168C | | | | | | | |
| D168E | 302 | 40x-95x | resistance likely | Yes | 1,2,3,6,7 | 20 | Clinical TE RAV (2,3,6) |
| D168F | | | Resistance possible | Yes | 2,3 | <8 | Clinical TE RAV (2,3) |
| D168G | 42 | 4.4x | likely susceptible | No | 1,3,6 | | Clinical SMV+P/R TE RAV (3) |
| D168H | 5655 | 368x | resistance likely | Yes | 1,6 | 2 | Clinical TE RAV (2,6) |
| D168I | 23203 | 1807x | resistance likely | | 1,6 | | |
| D168K | | | | | | | no specific Clincial RAS indicated (2) |
| D168L | | | | | | | no specific Clincial RAS indicated (2) |
| D168N | 79 | 6.6x | resistance likely | Yes | 1,6 | | Clinical VF RAV (4) |
| D168Q | | <700x | resistance likely | Yes | 4 | | Clinical VF RAV (4) |
| D168S | | | | | | | |
| D168T | 4089 | 308x | resistance likely | Yes | 1,6 | 3 | Clinical TE RAV (2,6) |
| D168V | 17917 | 2591x | resistance likely | Yes | 1,2,3,6,7 | 52 | Clinical TE RAV (2,3,6) |
| D168Y | 6238 | 666x | resistance likely | Yes | 1,3,6 | | Clinical TE RAV (3) |
| V170A | 22 | 4.7x | likely susceptible | | 6,1 | | |
| V170T | 52 | 5.4x | Resistance possible | | 1,4,6 | <8 | |
| V170I | | | Resistance possible | Yes | 6 | 2 | Clincal VF RAS , 50% NGS (6) |
| S174F | | | Resistance possible | Yes | 6 | 7 | Clincial TE RAV (6) |
| M175L | | | | | | | |
| E176G | | | | | | | |
| T185S | | | | | | | |
| H246Y | | | | | | 1 | |
| IT269S | | | | | | 1 | |
| S280P | | | Resistance possible | Yes | 6 | 1 | Clincial TE RAS, 30% NGS (6) |
| I288M | | | | | | 1 | |
| N335G | | | | | | 1 | |
| T344A | | | Resistance possible | Yes | 6 | 2 | Clinical TE RAS, 50% NGS (6) |
| E357K | | | | | | | |
| T358F | | | Resistance possible | Yes | 6 | 2 | Clinical TE RAS, 94% NGS (6) |
| G383S | | | Resistance possible | Yes | 6 | 2 | Clinical TE RAS, 50% NGS (6) |
| S403T | | | | | | 1 | |
| I426V | | | Resistance possible | Yes | 6 | 4 | Clincial TE RAV (6) |
| T448A | | | Resistance possible | Yes | 6 | 4 | Clincial TE RAV (6) |
| M470R | | | | | 6 | 1 | Clincial TE EAS, 52% NGS (6) |
| I472V | | | Resistance possible | Yes | 6 | 2 | Clinical TE RAS (6) |
| V535A | | | Resistance possible | Yes | 6 | 2 | Clincial TE RAV (6) |
| P574A | | | Resistance possible | Yes | 6 | 2 | Clinicla TE RAS, 98%&79% NGS (6) |
| P574S | | | Resistance possible | Yes | 6 | 2 | Clinical TE RAS, 50% NGS (6) |
| V629I | | | Resistance possible | Yes | 6 | 1 | novel RAS, 97% NGS (6) |
| V36A+V55A | | | | | | | |
| V36A+T54A | | | | | | | |
| V36M+R155K | | | | | | | |
| V36M+R155K | | | | | | | |
| V36M+A156S | | | | | | | |
| Q41R+Q80R | | | | | | | |
| Q41R+D168V | | | | | | | |
| F43S+Q80R | 1815 | 286x | resistance likely | | 1,6 | | |
| F43S+D168E | 3607 | 694x | resistance likely | | 1,6 | | |
| T54S+V170T | | | | | | | |
| T54S+M175L | | | | | | | |
| T54S+Y56F | | | | | | | |
| T54A+Q80L | | | | | | | |
| Y56F+D168Y | | | | | | | |
| Y56F+D168E | | | | | | | |
| Y56F+Q80L | | | | | | | |
| Y56F+Q80R | | | | | | | |
| Y56F+S122N | | | | | | | |
| Y56F+V170I | | | | | | | |
| Y56F+V170T | | | | | | | |
| Y56H+D168A | | | | | | | |
| Y56H+D168V | | | | | | | |
| Y56H+D168V | | | | | | | |
| Y56H+D168Y | | | | | | | |
| Y65H+D168E | | | | | | | |
| Q80H+D168E | 1362 | 163x | resistance likely | Yes | 1,6 | | Clinical TE RAV (2) |
| Q80K+D168Y | | | | | | | |
| Q80K+D168V | | | | | | | |
| Q80K+R155K | 4647 | 364x | resistance likely | | 1,6 | | |
| Q80L+D168V | | | | | | | |
| Q80R+D168A | 16867 | 2655x | resistance likely | Yes | 1,6 | | Clinical TE RAV (2) |
| Q80R+D168E | 5902 | 412x | resistance likely | | 1 | | Clinical TE RAV (2) |
| Q80R+R155K | 2853 | 270x | resistance likely | | 1,6 | | |
| P89L+A156V | | | | | | | |
| P89L+A156T | | | | | | | |
| S122T+V170I | | | | | | | |
| R155K+D168V | | 2596x | resistance likely | Yes | 6 | 1 | Clinical TE RAS (6) |
| R155K+V170A | | | | | | | |
| R155W+A156G | | | | | | | |
| R155X+D168X | | | | | | | |
| A156G+D168N | | | | | | | |
| A156T+D168V | | | | | | | |
| A156V+D168V | | | | | | | |
| A156V+E176G | | | | | | | |
| D168N+V170I | | | | | | | |
| T54S+Q80L+V170I | | | | | | | |
| Y56F+S122T+V170I | | | | | | | |
| Y56F+S122N+V170I | | | | | | | |
| R155W+A156G+D168N | | | | | | | |
| NS4A V23A | | | | | | | |
| 1. Lenz et al. (2010) AAC 54(5):1878-1887 |
| 2.Olysio US Product Label (2014) {SMV+SOF trials] |
| 3. Lontok et al. (2015) HEPATOLOGY 62:1623-1632) |
| 4. Sorbo et al. (2018) Drug Resistance Update (in press) https://doi.org/10.1016/j.drup.2018.01.004 |
| 5. Verbinnen et al (2010) J. Virology 84(21):11124-11133. PMCID:2953167 |
| 6. FDA Microbiology/Virology Reviews simeprevir_205123Orig1s000MicroR |
| 7. FDA Vosevi Microbiology Reviews 209195Orig1s000MicroR |
Telaprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (1b_con1) | | | likely susceptible | | 1 | |
| S7A | | | | | | |
| R24W | | | | | | |
| V36A | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V36G | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V36I | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V36L | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V36M | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V36S | | | | | | |
| A39T | | | | | | |
| Q41L | | | | | | |
| Q41R | | | | | | |
| F43S | | | | | | |
| F43I | | | | | | |
| F43L | | | | | | |
| F43V | | | | | | |
| T46S | | | | | | |
| V48I | | | | | | |
| T54A | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| T54C | | | | | | |
| T54G | | | | | | |
| T54S | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V55A | | | | | | |
| V55I | | | | | | |
| Y56H | | | | | | |
| Y56F | | | | | | |
| Y56L | | | | | | |
| S61L | | | | | | |
| V71I | | | | | | |
| N77S | | | | | | |
| Q80G | | | | | | |
| Q80H | | | | | | |
| Q80I | | January 1, 1970 | | | | |
| Q80K | | | | | | |
| Q80L | | | | | | |
| Q80M | | | | | | |
| Q80R | | | | | | |
| Q86R | | | | | | |
| P89L | | | | | | |
| T95S | | | | | | |
| V107I | | | | | | |
| R109K | | | | | | |
| R117C | | | | | | |
| S122A | | | | | | |
| S122D | | | | | | |
| S122G | | | | | | |
| S122I | | | | | | |
| S122N | | | | | | |
| S122R | | | | | | |
| S122T | | | | | | |
| V132I | | | | | | |
| V132L | | | | | | |
| S138T | | | | | | |
| S138P | | | | | | |
| V150A [Conflicting WT, not used in algorithm] | | | | | | |
| R155C | | | | | | |
| R155E | | | | | | |
| R155G | | | | | | |
| R155I | | | | | | |
| R155K | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| R155N | | | | | | |
| R155M | | | | | | |
| R155Q | | | | | | |
| R155S | | | | | | |
| R155T | | | | | | |
| R155W | | | | | | |
| A156F | | | resistance likely | | | |
| A156G | | | | | | |
| A156S | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| A156T | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| A156V | | | resistance likely | Yes | 1 | Clinical TE RAV (1) |
| V158I | | | | | | |
| A166S | | | | | | |
| D168A | | | | | | |
| D168C | | | | | | |
| D168E | | | | | | |
| D168F | | | | | | |
| D168G | | | | | | |
| D168H | | | | | | |
| D168I | | | | | | |
| D168K | | | | | | |
| D168L | | | | | | |
| D168N | | | | | | |
| D168Q | | | | | | |
| D168S | | | | | | |
| D168T | | | | | | |
| D168V | | | | | | |
| D168Y | | | | | | |
| V170A | | | | | | |
| V170T | | | | | | |
| V170I | | | | | | |
| S174F | | | | | | |
| M175L | | | | | | |
| E176G | | | | | | |
| T185S | | | | | | |
| H246Y | | | | | | |
| IT269S | | | | | | |
| S280P | | | | | | |
| I288M | | | | | | |
| N335G | | | | | | |
| T344A | | | | | | |
| E357K | | | | | | |
| T358F | | | | | | |
| G383S | | | | | | |
| S403T | | | | | | |
| I426V | | | | | | |
| T448A | | | | | | |
| M470R | | | | | | |
| I472V | | | | | | |
| V535A | | | | | | |
| P574A | | | | | | |
| P574S | | | | | | |
| V629I | | | | | | |
| V36A+V55A | | | | | | |
| V36A+T54A | | | | | | |
| V36M+R155K | | | | | | |
| V36M+R155K | | | | | | |
| V36M+A156S | | | | | | |
| Q41R+Q80R | | | | | | |
| Q41R+D168V | | | | | | |
| F43S+Q80R | | | | | | |
| F43S+D168E | | | | | | |
| T54S+V170T | | | | | | |
| T54S+M175L | | | | | | |
| T54S+Y56F | | | | | | |
| T54A+Q80L | | | | | | |
| Y56F+D168Y | | | | | | |
| Y56F+D168E | | | | | | |
| Y56F+Q80L | | | | | | |
| Y56F+Q80R | | | | | | |
| Y56F+S122N | | | | | | |
| Y56F+V170I | | | | | | |
| Y56F+V170T | | | | | | |
| Y56H+D168A | | | | | | |
| Y56H+D168V | | | | | | |
| Y56H+D168V | | | | | | |
| Y56H+D168Y | | | | | | |
| Y65H+D168E | | | | | | |
| Q80H+D168E | | | | | | |
| Q80K+D168Y | | | | | | |
| Q80K+D168V | | | | | | |
| Q80K+R155K | | | | | | |
| Q80L+D168V | | | | | | |
| Q80R+D168A | | | | | | |
| Q80R+D168E | | | | | | |
| Q80R+R155K | | | | | | |
| P89L+A156V | | | | | | |
| P89L+A156T | | | | | | |
| S122T+V170I | | | | | | |
| R155K+D168V | | | | | | |
| R155K+V170A | | | | | | |
| R155W+A156G | | | | | | |
| R155X+D168X | | | | | | |
| A156G+D168N | | | | | | |
| A156T+D168V | | | | | | |
| A156V+D168V | | | | | | |
| A156V+E176G | | | | | | |
| D168N+V170I | | | | | | |
| T54S+Q80L+V170I | | | | | | |
| Y56F+S122T+V170I | | | | | | |
| Y56F+S122N+V170I | | | | | | |
| R155W+A156G+D168N | | | | | | |
| NS4A V23A | | | | | | |
| 1. Lontok et al. (2015) HEPATOLOGY 62:1623-1632) |
Voxilaprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Replication Capacity (%WT) | Comments |
| WT (1b_con1) | 0.51 (SD 0.26) | 1x | likely susceptible | | 3 | 100 (4) | mean of 87 clinical isolates |
| S7A | | | | | | | |
| R24W | | | | | | | |
| V36A | | 2.5-20x | Resistance possible | | 3 | | |
| V36G | | | | | | | |
| V36I | | | likely susceptible | | 3 | | |
| V36L | | | | | | | |
| V36M | | 3.4x | Resistance possible | | 3,1 | | |
| V36S | | | likely susceptible | | 3 | | |
| A39T | | | | | | | |
| Q41L | | | | | | | |
| Q41R | | | | | | | |
| F43S | | | | | | | |
| F43I | | | | | | | |
| F43L | | | | | | | |
| F43V | | | | | | | |
| T46S | | | | | | | |
| V48I | | | | | | | |
| T54A | | 1.6x | likely susceptible | | 4 | | |
| T54C | | | | | | | |
| T54G | | | | | | | |
| T54S | | <2.3x | likely susceptible | | 4 | | |
| V55A | | 1.7x | likely susceptible | | 3 | | |
| V55I | | | | | | | |
| Y56H | unfit | | | | 3 | | |
| Y56F | | | likely susceptible | | 3 | | |
| Y56L | | | | | | | |
| S61L | | | | | | | |
| V71I | | | | | | | |
| N77S | | | | | | | |
| Q80G | | | | | | | |
| Q80H | | | | | | | |
| Q80I | | | | | | | |
| Q80K | | 0.9x | likely susceptible | | 3 | | |
| Q80L | | 1.3x | likely susceptible | | 3 | | |
| Q80M | | | likely susceptible | | 3 | | |
| Q80R | | 1.9x | likely susceptible | | 3 | | |
| Q86R | | | | | | | |
| P89L | | | | | | | |
| T95S | | | | | | | |
| V107I | | | likely susceptible | | 3 | | |
| R109K | | | | | | | |
| R117C | | | | | | | |
| S122A | | | | | | | |
| S122D | | 2.5-20x | Resistance possible | | 3,1 | | |
| S122G | | | likely susceptible | | 3 | | |
| S122I | | | | | | | |
| S122N | | | likely susceptible | | 3 | | |
| S122R | | | | | | | |
| S122T | | | likely susceptible | | 3 | | |
| V132I | | | | | | | |
| V132L | | | | | | | |
| S138T | | | | | | | |
| S138P | | | | | | | |
| V150A [Conflicting WT, not used in algorithm] | | | | | | | |
| R155C | | | | | | | |
| R155E | | | | | | | |
| R155G | unfit | | | | 3 | | |
| R155I | | | | | | | |
| R155K | | 1.5x | likely susceptible | | 3 | | |
| R155N | | | | | | | |
| R155M | | | | | | | |
| R155Q | | | | | | | |
| R155S | | | | | | | |
| R155T | | | | | | | |
| R155W | | 95x | resistance likely | | 3,1 | | |
| A156F | | >2.5x | | | 1 | | |
| A156G | | >2.5x | | | 1 | | |
| A156S | | 2.5-20x | Resistance possible | | 3,1 | | |
| A156T | | 552x | resistance likely | | 3,2,4 | 40.5 (4) | |
| A156V | | 458 | resistance likely | | 3,2,4 | 25.5 (4) | |
| V158I | | | likely susceptible | | 3 | | |
| A166S | | | likely susceptible | | 3 | | |
| D168A | | | likely susceptible | | 3 | | |
| D168C | | | | | | | |
| D168E | | | likely susceptible | | 3 | | |
| D168F | | | | | | | |
| D168G | | | likely susceptible | | 3 | | |
| D168H | | | | | | | |
| D168I | | | | | | | |
| D168K | | | | | | | |
| D168L | | | | | | | |
| D168N | | | | | | | |
| D168Q | | | | | | | |
| D168S | | | | | | | |
| D168T | | | | | | | |
| D168V | | 2.5-20x | Resistance possible | | 3,1 | | |
| D168Y | | 2.5-20x | Resistance possible | | 3,1 | | |
| V170A | | 2.5-20x | Resistance possible | | 3,1 | | |
| V170T | | | likely susceptible | | 3 | | |
| V170I | | | likely susceptible | | 3 | | |
| S174F | | | | | | | |
| M175L | | | likely susceptible | | 3 | | |
| E176G | | | | | | | |
| T185S | | | | | | | |
| H246Y | | | | | | | |
| IT269S | | | | | | | |
| S280P | | | | | | | |
| I288M | | | | | | | |
| N335G | | | | | | | |
| T344A | | | | | | | |
| E357K | | | | | | | |
| T358F | | | | | | | |
| G383S | | | | | | | |
| S403T | | | | | | | |
| I426V | | | | | | | |
| T448A | | | | | | | |
| M470R | | | | | | | |
| I472V | | | | | | | |
| V535A | | | | | | | |
| P574A | | | | | | | |
| P574S | | | | | | | |
| V629I | | | | | | | |
| V36A+V55A | | | likely susceptible | | 3 | | |
| V36A+T54A | | | | | | | |
| V36M+R155K | | | | | | | |
| V36M+R155K | | | | | | | |
| V36M+A156S | | 2.5-20x | Resistance possible | | 3,1 | | |
| Q41R+Q80R | | | | | | | |
| Q41R+D168V | | | | | | | |
| F43S+Q80R | | | | | | | |
| F43S+D168E | | | | | | | |
| T54S+V170T | | | likely susceptible | | 3 | | |
| T54S+M175L | | | likely susceptible | | 3 | | |
| T54S+Y56F | | | likely susceptible | | 3 | | |
| T54A+Q80L | | | likely susceptible | | 3 | | |
| Y56F+D168Y | | 0.8 | likely susceptible | | 3 | | |
| Y56F+D168E | | | | | | | |
| Y56F+Q80L | | | | | | | |
| Y56F+Q80R | | 1.1 | likely susceptible | | 3 | | |
| Y56F+S122N | | 3.4 | Resistance possible | | 3 | | |
| Y56F+V170I | | 1.6 | likely susceptible | | 3 | | |
| Y56F+V170T | | 1.1 | likely susceptible | | 3 | | |
| Y56H+D168A | | | | | | | |
| Y56H+D168V | | | | | | | |
| Y56H+D168V | | | | | | | |
| Y56H+D168Y | | | | | | | |
| Y65H+D168E | | | | | | | |
| Q80H+D168E | | | | | | | |
| Q80K+D168Y | | | | | | | |
| Q80K+D168V | | | | | | | |
| Q80K+R155K | | | | | | | |
| Q80L+D168V | | | likely susceptible | | 3 | | |
| Q80R+D168A | | | | | | | |
| Q80R+D168E | | | likely susceptible | | 3 | | |
| Q80R+R155K | | | | | | | |
| P89L+A156V | | | | | | | |
| P89L+A156T | | | | | | | |
| S122T+V170I | | | likely susceptible | | 3 | | |
| R155K+D168V | | | | | | | |
| R155K+V170A | | | | | | | |
| R155W+A156G | | | | | | | |
| R155X+D168X | | | | | | | |
| A156G+D168N | | | | | | | |
| A156T+D168V | | | | | | | |
| A156V+D168V | | | | | | | |
| A156V+E176G | | | | | | | |
| D168N+V170I | | 0.7 | likely susceptible | | 3 | | |
| T54S+Q80L+V170I | | | | | | | |
| Y56F+S122T+V170I | | 1.7 | likely susceptible | | 3 | | |
| Y56F+S122N+V170I | | 3.3 | Resistance possible | | 3 | | |
| R155W+A156G+D168N | | | | | | | |
| NS4A V23A | | | | | | | |
| 1. Sarrazin C, et al. 2017. Gastroenterology 152: S1062 |
| 2. Vosevi US Product Label 2017 |
| 3. Dvory-Sobol H et al 2017 AASLD. http://www.natap.org/2017/AASLD/AASLD_29.htm |
| 4. FDA Vosevi Microbiology Reviews 209195Orig1s000MicroR |
