NS3 GT4
Download full data set for GT4
Asunaprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (4a_ED43) | 1.8-7.6 | 1x | likely susceptible | | 1 | |
| WT (GT4d) [not used as reference in algorithm] | | | | | | |
| K26R | | | | | | |
| V36M | | | | | | |
| Q41H | | | | | | |
| Q41R | | | | | | |
| F43L | | | | | | |
| L44M | | | | | | |
| T54G | | | | | | |
| T54S | | | | | | |
| Y56H | | | | | | |
| P67S | | | | | | |
| N77S | | | | | | |
| Q80K | | | | | | |
| G90R | | | | | | |
| V107I | | | | | | |
| T122A | | | | | | |
| T122N | | | | | | |
| T122S | | | | | | |
| T122V | | | | | | |
| T122G | | | | | | |
| T122R | | | | | | |
| I132L | | | | | | |
| I132V | | | | | | |
| R155C | | | | | | |
| R155G | | | | | | |
| R155K | | | | | | |
| R155Q | | | | | | |
| R155W | | | | | | |
| A156G | | | | | | |
| A156H | | | | | | |
| A156K | | | | | | |
| A156L | | | | | | |
| A156M | | | | | | |
| A156S | | | | | | |
| A156T | | | | | | |
| A156V | | | | | | |
| V158I | | | | | | |
| G162R | | | | | | |
| A166S | | | | | | |
| D168A | | | | | | |
| D168C | | | | | | |
| D168E | | | | | | |
| D168F | | | | | | |
| D168G | | | | | | |
| D168H | | | | | | |
| D168I | | | | | | |
| D168K | | | | | | |
| D168L | | | | | | |
| D168N | | | | | | |
| D168R | | | | | | |
| D168T | | | | | | |
| D168V | | | | | | |
| D168Y | | | | | | |
| V170I | | | | | | |
| V170L | | | | | | |
| Q178R | | | | | | |
| T185S | | | | | | |
| T382S | | | | | | |
| V36M+A156T | | | | | | |
| F43S+Q80K | | | | | | |
| Y56H+D168A | | | | | | |
| Y56H+D168V | | | | | | |
| P67S+A156T | | | | | | |
| G90R+A156T | | | | | | |
| R155Q+D168V | | | | | | |
| G162R+D168A | | | | | | |
| G162R+D168V | | | | | | |
| F43S+Q80K+D168Y | | | | | | |
| 1. Sunvepra Canadian Prodcut Monograph 2016 |
Glecaprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (4a_ED43) | 2.8 | 1x | likely susceptible | | 1 | clinical isolate=0.3 (0.05-3.8) |
| WT (GT4d) [not used as reference in algorithm] | | | | | | |
| K26R | | | | | | |
| V36M | | | | | | |
| Q41H | | | | | | |
| Q41R | | | | | | |
| F43L | | | | | | |
| L44M | | | | | | |
| T54G | | | | | | |
| T54S | | | | | | |
| Y56H | 0.69 | 4.6x | resistance possible | | 1 | GT4d |
| P67S | 0.65 | 1x | likely susceptible | | 1 | |
| N77S | | | | | | |
| Q80K | | | | | | |
| G90R | 4.7 | 7x | resistance possible | | 1 | |
| V107I | | | | | | |
| T122A | | | | | | |
| T122N | | | | | | |
| T122S | | | | | | |
| T122V | | | | | | |
| T122G | | | | | | |
| T122R | | | | | | |
| I132L | | | | | | |
| I132V | | | | | | |
| R155C | 1.7 | 2.6x | resistance possible | | 1 | |
| R155G | | | | | | |
| R155K | | | | | | |
| R155Q | | | | | | |
| R155W | | | | | | |
| A156G | | | | | | |
| A156H | | | | | | |
| A156K | | | | | | |
| A156L | | | | | | |
| A156M | | | | | | |
| A156S | | | | | | |
| A156T | 962 | 1436x | resistance likely | | 1 | |
| A156V | 2081 | 3106x | resistance likely | | 1 | |
| V158I | | | | | | |
| G162R | | | | | | |
| A166S | | | | | | |
| D168A | | | | | | |
| D168C | | | | | | |
| D168E | | | | | | |
| D168F | | January 1, 1970 | | | | |
| D168G | | | | | | |
| D168H | 14.6 | 22x | resistance likely | | 1 | |
| D168I | | | | | | |
| D168K | | | | | | |
| D168L | | | | | | |
| D168N | | | | | | |
| D168R | | | | | | |
| D168T | | | | | | |
| D168V | 6.5 | 9.7x | resistance possible | | 1 | GT4d (1.9x) |
| D168Y | | | | | | |
| V170I | | | | | | |
| V170L | | | | | | |
| Q178R | | | | | | |
| T185S | | | | | | |
| T382S | | | | | | |
| V36M+A156T | | | | | | |
| F43S+Q80K | | | | | | |
| Y56H+D168A | | | | | | |
| Y56H+D168V | 8.7 | 58x | resistance likely | | 1 | GT4d |
| P67S+A156T | 1187 | 1772x | resistance likely | | 1 | |
| G90R+A156T | 1343 | 2004x | resistance likely | | 1 | |
| R155Q+D168V | | | | | | |
| G162R+D168A | | | | | | |
| G162R+D168V | | | | | | |
| F43S+Q80K+D168Y | | | | | | |
| 1. 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 |
| WT (4a_ED43) | 0.2 | 1x | likely susceptible | | 1,2 | |
| WT (GT4d) [not used as reference in algorithm] | | | | | | |
| K26R | | | | | | |
| V36M | | | | | | |
| Q41H | | | | | | |
| Q41R | | | | | | |
| F43L | | | | | | |
| L44M | | | | | | |
| T54G | | | | | | |
| T54S | | | | | | |
| Y56H | | | | | | |
| P67S | | | | | | |
| N77S | | | | | | |
| Q80K | | | | | | |
| G90R | | | | | | |
| V107I | | | resistance possible | Yes | 2 | Clinical TE RAV (2) |
| T122A | | | | | | |
| T122N | | | | | | |
| T122S | | | | | | |
| T122V | | | | | | |
| T122G | | | | | | |
| T122R | | | | | | |
| I132L | | | | | | |
| I132V | | | | | | |
| R155C | | | | | | |
| R155G | | | | | | |
| R155K | | | | | | |
| R155Q | | | | | | |
| R155W | | | | | | |
| A156G | | | | | | |
| A156H | | | | | | |
| A156K | | | | | | |
| A156L | | | | | | |
| A156M | | | resistance possible | Yes | 2,1,3,5 | Clinical TE RAV (2,1,3,5) |
| A156S | | | | | | |
| A156T | | | resistance possible | Yes | 2,1,3,5 | Clinical TE RAV (2,1,3,5) |
| A156V | | | resistance possible | Yes | 2,1,3,5 | Clinical TE RAV (2,1,3,5) |
| V158I | | | | | | |
| G162R | | 1x | likely susceptible | | 4,3 | enhance replicative fitness by 4x |
| A166S | | | | | | |
| D168A | 96 | 320x | resistance likely | Yes | 1,2,3,4,5 | Clinical TE RAV (2,3,5) |
| D168C | | | | | | |
| D168E | | | resistance possible | Yes | 5 | Clinical VF RAS (5) |
| D168F | | | | | | |
| D168G | unfit | | resistance possible | Yes | 1,2,3,4,5 | Clinical TE RAV (2,1,3,5) |
| D168H | | | | | | |
| D168I | | | | | | |
| D168K | | | | | | |
| D168L | | | | | | |
| D168N | | | | | | |
| D168R | | | | | | |
| D168T | | | | | | |
| D168V | | 110x | resistance likely | | 1,2,4 | in G162R_D168V |
| D168Y | | | | | | |
| V170I | | | resistance possible | Yes | 2,3,5 | Clinical TE RAV (2,3,5) |
| V170L | | | | | | |
| Q178R | | | | | | |
| T185S | | | | | | |
| T382S | | | | | | |
| V36M+A156T | | | | | | |
| F43S+Q80K | | | | | | |
| Y56H+D168A | | | | | | |
| Y56H+D168V | | | | | | |
| P67S+A156T | | | | | | |
| G90R+A156T | | | | | | |
| R155Q+D168V | | | | | | |
| G162R+D168A | | 320x | resistance likely | | 3 | |
| G162R+D168V | | 110x | resistance likely | | 3 | |
| F43S+Q80K+D168Y | | | | | | |
| 1. Zapatier Canadian Product Label |
| 2. Zepatier US Product Label |
| 3. FDA Zepatier Microbiology/Virology Review_208261Orig1s000MicroR |
| 4. Asante-Appiah E, et al. 2017. Antimicrobial Agents and Chemotherapy: AAC-00363 |
| 5. Asselah T et al. Liver International Liver Int. 2018;00:1–9. https://doi.org/10.1111/liv.13727 |
Paritaprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (4a_ED43) | 0.09 | 1x | likely susceptible | | 1 ,3 | |
| WT (GT4d) [not used as reference in algorithm] | 0.015 | 1x | likely susceptible | | 1 ,3 | |
| K26R | | | | | | |
| V36M | | | | | | |
| Q41H | | | | | | |
| Q41R | | | | | | |
| F43L | | | | | | |
| L44M | | | | | | |
| T54G | | | | | | |
| T54S | | | | | | |
| Y56H | | 8x | resistance likely | Yes | 1 ,3,2 ,4 | Clinical TE RAV in GT4d(1,3,4), VF RAS(2) |
| P67S | | | | | | |
| N77S | | | | | | |
| Q80K | | | | | | |
| G90R | | | | | | |
| V107I | | | | | | |
| T122A | | | | | | |
| T122N | | | | | | |
| T122S | | | | | | |
| T122V | | | | | | |
| T122G | | | | | | |
| T122R | | | | | | |
| I132L | | | | | | |
| I132V | | | | | | |
| R155C | | 59x | resistance likely | | 4,3,1 | |
| R155G | | | | | | |
| R155K | | | | | | |
| R155Q | | | | | | |
| R155W | | | | | | |
| A156G | | | | | | |
| A156H | | | | | | |
| A156K | | | | | | |
| A156L | | | | | | |
| A156M | | | | | | |
| A156S | | | | | | |
| A156T | | 40x | resistance likely | | 4,1, 3 | |
| A156V | | 155x | resistance likely | | 4,1, 3 | |
| V158I | | | | | | |
| G162R | | | | | | |
| A166S | | | | | | |
| D168A | | | | | | |
| D168C | | | | | | |
| D168E | | | | | | |
| D168F | | | | | | |
| D168G | | | | | | |
| D168H | | 252x | resistance likely | | 4,1, 3 | |
| D168I | | | | | | |
| D168K | | | | | | |
| D168L | | | | | | |
| D168N | | | | | | |
| D168R | | | | | | |
| D168T | | | | | | |
| D168V | | 313x | resistance likely | Yes | 1,2, 3,4 | Clinical TE RAV in Gt4d bckgd (1,3,4) ; clinical VF RAV (2) |
| D168Y | | | | | | |
| V170I | | | | | | |
| V170L | | | | | | |
| Q178R | | | | | | |
| T185S | | | | | | |
| T382S | | | | | | |
| V36M+A156T | | | | | | |
| F43S+Q80K | | | | | | |
| Y56H+D168A | | | | | | |
| Y56H+D168V | 188 | 12,533x | resistance likely | Yes | 1 | clinical VF RAV (1,3), GT4d |
| P67S+A156T | | | | | | |
| G90R+A156T | | | | | | |
| R155Q+D168V | | | | | | |
| G162R+D168A | | | | | | |
| G162R+D168V | | | | | | |
| F43S+Q80K+D168Y | | | | | | |
| 1. Technivie US Product Label Jan 28, 2016 |
| 2. Lontok et al. (2015) Hepatology in press |
| 3. Technivie Canadian Product Monograph Nov 24, 2015 |
| 4. FDA NDA Microbiology Virology Reviews Technive_207931Orig1s000MedR |
Simeprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (4a_ED43) | | | | | | |
| WT (GT4d) [not used as reference in algorithm] | | | | | | |
| K26R | | | | | | |
| V36M | | | | | | |
| Q41H | | | | | | |
| Q41R | | | | | | |
| F43L | | | | | | |
| L44M | | | | | | |
| T54G | | | | | | |
| T54S | | | | | | |
| Y56H | | | | | | |
| P67S | | | | | | |
| N77S | | | | | | |
| Q80K | | | | | | |
| G90R | | | | | | |
| V107I | | | | | | |
| T122A | | | | | | |
| T122N | | | | | | |
| T122S | | | | | | |
| T122V | | | | | | |
| T122G | | | | | | |
| T122R | | | | | | |
| I132L | | | | | | |
| I132V | | | | | | |
| R155C | | | | | | |
| R155G | | | | | | |
| R155K | | 163x | resistance likely | | 1 | |
| R155Q | | | | | | |
| R155W | | | | | | |
| A156G | | 26x | resistance likely | | 1 | |
| A156H | | | | | | |
| A156K | | | | | | |
| A156L | | | | | | |
| A156M | | 0.6x | likely susceptible | | 1 | |
| A156S | | | | | | |
| A156T | | | | | | |
| A156V | | | | | | |
| V158I | | | | | | |
| G162R | | | | | | |
| A166S | | | | | | |
| D168A | | | | | | |
| D168C | | | | | | |
| D168E | | | | | | |
| D168F | | January 1, 1970 | | | | |
| D168G | | | | | | |
| D168H | | | | | | |
| D168I | | | | | | |
| D168K | | | | | | |
| D168L | | | | | | |
| D168N | | | | | | |
| D168R | | | | | | |
| D168T | | | | | | |
| D168V | | | | | | |
| D168Y | | | | | | |
| V170I | | | | | | |
| V170L | | | | | | |
| Q178R | | | | | | |
| T185S | | | | | | |
| T382S | | | | | | |
| V36M+A156T | | | | | | |
| F43S+Q80K | | | | | | |
| Y56H+D168A | | | | | | |
| Y56H+D168V | | | | | | |
| P67S+A156T | | | | | | |
| G90R+A156T | | | | | | |
| R155Q+D168V | | | | | | |
| G162R+D168A | | | | | | |
| G162R+D168V | | | | | | |
| F43S+Q80K+D168Y | | | | | | |
| 1. Jensen et al. 2015. AAC 59(12):7426-36 |
Voxilaprevir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Replication Capacity (%WT) | Comments |
| WT (4a_ED43) | 0.65 (SD 0.37) | 1x | likely susceptible | | 3 | 100 (4) | mean of 81 clinical isolates |
| WT (GT4d) [not used as reference in algorithm] | | | | | | | |
| K26R | | | | | | | |
| V36M | | | | | | | |
| Q41H | | | likely susceptible | | 3 | | |
| Q41R | | 2.5-20x | resistance possible | | 3,1 | | |
| F43L | unfit | | | | 3 | | |
| L44M | | <2x | likely susceptible | | 4 | | |
| T54G | | | | | | | |
| T54S | | | likely susceptible | | 3,4 | | |
| Y56H | | | | | | | |
| P67S | | | | | | | |
| N77S | | | | | | | |
| Q80K | | | | | | | |
| G90R | | | | | | | |
| V107I | | | | | | | |
| T122A | | | likely susceptible | | 3 | | |
| T122N | | | likely susceptible | | 3 | | |
| T122S | | | likely susceptible | | 3,4 | | |
| T122V | | | likely susceptible | | 3 | | |
| T122G | | | | | | | |
| T122R | | | | | | | |
| I132L | | <2x | likely susceptible | | 4 | | |
| I132V | | <2x | likely susceptible | | 4 | | |
| R155C | | | likely susceptible | | 3 | | |
| R155G | unfit | | | | 3 | | |
| R155K | | | likely susceptible | | 3 | | |
| R155Q | unfit | | | | 3 | | |
| R155W | unfit | | | | 3 | | |
| A156G | | >2.5x | | | 1 | | |
| A156H | | | | | | | |
| A156K | | | | | | | |
| A156L | | >224x | resistance likely | | 4,2,3 | 793 (4) | |
| A156M | | | | | 1 | | |
| A156S | | | | | 1 | | |
| A156T | | 143x | resistance likely | | 4,2,3 | 137 (4) | |
| A156V | | >309x | resistance likely | | 4,2,3 | 30.9 (4) | |
| V158I | | | | | | | |
| G162R | | | | | | | |
| A166S | | | likely susceptible | | 3 | | |
| D168A | | | | | | | |
| D168C | | | | | | | |
| D168E | | 2.5-20x | resistance possible | | 3,1 | | |
| D168F | | January 1, 1970 | | | | | |
| D168G | | | | | | | |
| D168H | | | | | | | |
| D168I | | | | | | | |
| D168K | | | likely susceptible | | 3 | | |
| D168L | | | | | | | |
| D168N | | | | | | | |
| D168R | | | | | | | |
| D168T | | 2.5-20x | resistance possible | | 3,1 | | |
| D168V | | 2.5-20x | resistance possible | | 3,1 | | |
| D168Y | | | | | | | |
| V170I | | | likely susceptible | | 3,5 | | |
| V170L | | | likely susceptible | | 3 | | |
| Q178R | | | | | | | |
| T185S | | | resistance possible | Yes | 4 | | clinical TE RAV (4) |
| T382S | | | resistance possible | Yes | 4 | | clinical TE RAV (4) |
| V36M+A156T | | | | | | | |
| F43S+Q80K | unfit | | | | 3 | | |
| Y56H+D168A | | | | | | | |
| Y56H+D168V | | | | | | | |
| P67S+A156T | | | | | | | |
| G90R+A156T | | | | | | | |
| R155Q+D168V | | 1x | likely susceptible | | 3 | | |
| G162R+D168A | | | | | | | |
| G162R+D168V | | | | | | | |
| F43S+Q80K+D168Y | | 1x | likely susceptible | | 3 | | |
| 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 |
