NS5a GT4
Download full data set for GT4
Daclatasvir
Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Replication Fitness (14) | Reference | DCV+P/R VF (#pts) | Comments |
WT (1b_con1) | 0.004 | 1x | likely susceptible | | | 1,4,5 | | 0.001-0.009 |
Q24K | | <2.5x | likely susceptible | | | 13 | | |
Q24R | | | | | | | | |
L28A | | | resistance possible | Yes | | 14 | 1 | Clinical TE RAS (14) |
L28M | | 1.3x | resistance possible | Yes | 122 | 3,10,13,14,15 | 3 | Clinical TE RAV(3,10,14) |
L28T | | | resistance possible | Yes | | 7 | | Clinical VF RAV(3) |
L28I | | 3x | likely susceptible | | 126 | 15 | | |
L28V | | 2.3x | likely susceptible | | 78 | 15,13 | | |
P29S | | | resistance possible | Yes | | 3 | 1 | Clinical VF RAV(3) |
P29del | | 1,666,666x | resistance likely | Yes | | 3,14 | 1 | Clinical VF RAV(3,14) |
R30G | | 100x | resistance likely | Yes | 65 | 15,3 | | Clinical VF RAV(3), DCV+P/R RAS(3) |
R30H | | 6.7x | resistance possible | Yes | 39 | 15,3,14 | 2 | Clinical VF RAV(3,14) |
R30K | | 1x | resistance possible | Yes | 261 | 15,13 | 1 | Clinical DCV+SOF VF RAV(14) |
R30L | | 0.3x | likely susceptible | No | 29 | 15,13 | 1 | Clinical DCV+P/R VF RAV(14) |
R30P | | | likely susceptible | No | | 3,14 | 1 | Clinical VF RAV(3,14) |
R30Q | | 0.7x | resistance possible | Yes | 91,24 | 15,14,3,13 | 4 | Clinical VF RAV(3,14), transient 1b replicon |
R30S | | | likely susceptible | No | | 14 | 1 | Clinical VF RAV(14) |
R30T | | <2.5x | likely susceptible | | | 13 | | |
L31F | | 5x | resistance possible | Yes | 146 | 3,2,10,14,15 | 2 | Clinical TE RAV(3,10,14) |
L31I | | 3x | resistance possible | Yes | 54 | 3,2,14,15 | 7 | Clinical VF RAV(3,14) |
L31K | | | | | | | | |
L31M | 0.006 | 3x | resistance possible | Yes | 99 | 14,4,3,12,15 | 12 | Clinical VF RAV(3,14), transient 1b replicon (14) |
L31T | | | | | | | | |
L31V | 0.053 | 28x | resistance likely | Yes | 158,55 | 1,4, 3, 6,5,14,15 | 16 | Clinical VF RAV(3,14) |
L31W | | 91x | resistance possible | | 191 | 14 | | |
P32F | | | | | | 7 | | EASL 2016 guidelines |
P32L | | 16x | likely susceptible | | 18 | 14,13 | | |
P32K | | | | | | | | |
P32R | | | | | | | | |
P32N | | | | | | | | |
P32K | | | | | | | | |
P32T | | | | Yes | | 3 | 1 | Clinical DCV+P/R VF RAV(3) |
P32S | | | | | | 7 | | EASL 2016 guidelines |
P32del | | >1,666,667x | resistance likely | Yes | 29.1 | 3,6,14,15 | 3 | Clinical VF RAV(3,14) |
F37L | | 1x | likely susceptible | | 151 | 14 | | |
Q54H | 0.002 | 1x | resistance possible | Yes | 83 | 4,14,15 | 14 | Clinical DCV+SOF VF RAS(14), transient 1b replicon (14) |
Q54N | 0.003 | 1x | likely susceptible | | 83 | 4,14,15 | | |
Q54L | | 0.3x | likely susceptible | | 80 | 15 | | |
Q54Y | | 1.3x | likely susceptible | No | 90 | 8,14,3,15 | 1 | Clinical VF RAV(3,14) |
P58A | | 0.7x | likely susceptible | | 118 | 15 | | |
P58D | | | | | | 7 | | EASL 2016 guidelines |
P58L | 0.004 | 1x | resistance possible | Yes | 37 | 8,15 | | Clinical DCV+P/R VF RAV(3) |
P58Q | | <2.5x | likely susceptible | | | 13 | | |
P58R | | <2.5x | likely susceptible | | | 13 | | |
P58S | | 1x | resistance possible | Yes | 121 | 3,8,14,15 | 5 | Clinical VF RAV(3,14), transient 1b replicon (14) |
P58T | | 1x | likely susceptible | | 203 | 15,13 | | |
Q62D | | | likely susceptible | No | | 3 | 1 | Clinical VF RAV(14,3) |
Q62E | | 1x | resistance possible | Yes | 99 | 14,8,4 | 2 | Clincial DCV+SOF VF RAS (14) |
Q62A | | 0.7x | likely susceptible | | 99 | 15 | | |
Q62H | | 1x | likely susceptible | | 68 | 15 | | |
Q62N | | 0.7x | likely susceptible | | 69 | 15 | | |
Q62R | | 1x | likely susceptible | | 39 | 15 | | |
Q62S | | 1x | likely susceptible | | 107 | 15 | | |
A92E | | 1.3x | resistance possible | Yes | 17 | 15,13,14 | 2 | Clinical VF RAV(14) |
A92V | | | | | | | 1 | |
A92K | | >100x | resistance likely | Yes | | 3,14 | 2 | Clinical VF RAV(3,14) |
A92P | | <2.5x | likely susceptible | | | 13 | | |
A92T | | 1x | likely susceptible | No | 60 | 13,14,15 | 1 | Clinical VF RAV(14) |
A92V | | 0.3x | likely susceptible | | 98 | 15,13 | | |
Y93C | | 3x | likely susceptible | No | 62 | 14,7,15 | 1 | Clinical TE RAS (14) |
Y93H | 0.049 | 30x | resistance likely | Yes | 27, 5 | 15,14,1,4,3, 6,5,8,10,12 | 23 | Clinical VF RAV(3,10,14), transient 1b replicon (14) |
Y93N | | 50x | resistance possible | No | 19 | 3,14,15 | | Clinical VF RAV(3) |
Y93F | | 0.7x | likely susceptible | | 436 | 13,15 | | |
Y93L | | <2.5x | likely susceptible | | | 13 | | |
Y93R | | | | | | | | |
Y93T | | | | | | | | |
Y93S | | 6.7x | | | 160 | 15,7 | | EASL 2016 guidelines |
V121I | | | | | | | | |
D320E | | 0.9x | likely susceptible | | | 9 | | |
L23F+L31F | | 13x | likely susceptible | | 65 | 14 | | |
Q24R+R30Q | | | | | | | | |
L28I+R30Q | | 6.7x | likely susceptible | | 33 | 15 | | |
L28M+L31F | | | | | | | | |
L28M+P32del | | | | | | | | |
L28M+R30L | | 1x | likely susceptible | | 49 | 15 | | |
L28M+R30Q | | 1x | likely susceptible | | 2 | 15 | | |
L28M+R30Q | | | | | | | | |
L28M+Y93H | | 1000x | resistance likely | Yes | 70 | 15,14 | | Clincal VF RAV (14) |
L28V+L31F | | | | | | | | |
L28V+R30Q | | 0.3x | likely susceptible | | 2 | 15 | | |
R30H+Y93H | | 2,667x | resistance likely | | 24 | 15 | | |
R30L+L31M | | 3x | likely susceptible | | 75 | 15 | | |
R30Q+L31M | | 16.7x | likely susceptible | | 71 | 15 | | |
R30Q+L31F | | 88x | resistance possible | | 224 | 14 | | |
R30Q+L31V | | | | | | | | |
R30Q+Q54H | | 0.3x | likely susceptible | | 231 | 15 | | |
R30Q+A92K | | 77,000x | resistance likely | | 49 | 15 | | |
R30Q+Y93H | | 200x | resistance likely | | 146 | 15 | | |
R30Q+Y93S | | 23.3 | resistance possible | | 224 | 15 | | |
L31F+A92E | | | | | | | | |
L31F+P32del | | 1,666,667x | resistance likely | | 12 | 15 | | |
L31F+P58L | | | | | | | | |
L31F+Q54H | | | | | | | | |
L31F+Y93H | | 5000x | resistance likely | | 29 | 15 | | |
L31IV+Y93H | | 33,677x | resistance likely | Yes | | 14 | | Clincal VF RAV (14) |
L31I+A92V | | 1x | likely susceptible | | 65 | 15 | | |
L31I+Y93H | | 2492x | resistance likely | Yes | 6 | 14,15 | | Clincail VF RAV (14) |
L31M+A92K | | 1,281,333x | resistance likely | | 26 | 15 | | |
L31M+P58L | 1.5 | 200x | resistance likely | Yes | 37 | 15,8 | | Clinical VF RAV (8) |
L31M+P58S | | 30x | resistance possible | | 36 | 15 | | |
L31M+Q54H | | 1.3x | likely susceptible | | 111 | 15 | | |
L31M+Y93C | | | | | | | | |
L31M+Y93H | 13.5 | 7105x | resistance likely | Yes | 49.9 | 3,4, 6,8,12,14,15 | | Clinical VF RAV (8,14) |
L31M+Y93N | | 28,666x | | | 16 | | | |
L31V+P32del | | >1,666,667x | resistance likely | Yes | 16 | 14,15 | | Clincal VF RAV (14) |
L31V+Y93H | 21.7 | 33,666x | resistance likely | Yes | 10 | 1,3, 4, 6,5,8,9,14,15 | | Clincal VF RAS (14) |
L31V+Y93N | | | | | | | | |
P32del+Y93H | not viable | not viable | | | | | | |
F37L+Y93H | | 19x | likely susceptible | | 34 | 14 | | |
Q54H+Q62E | | 0.3x | | | 137 | 15 | | |
Q54H+A92E | | | | | | | | |
Q54H+Y93H | 0.018 | 9.2x | resistance possible | Yes | 22 | 14,8,4,15 | | Clinical VF RAV (8) |
Q54H+Y93S | | 2.7x | likely susceptible | | 279 | 15 | | |
Q54Y+Y93H | 0.04 | 67x | resistance likely | Yes | 25 | 15,8 | | Clincial DCV+ASV VF RAV (8) |
P58A+Y93H | | | | | | | | |
P58L+Y93H | | 233x | resistance likely | | 24 | 15 | | |
P58S+A92T | | 0.3x | likely susceptible | | 43 | 15 | | |
P58S+Y93H | | | | | | | | |
Q62E+Y93H | | 33.3x | resistance possible | | 36 | 15 | | |
A92T+Y93H | | 33.3x | resistance possible | | 2 | 15 | | |
A92V+Y93H | | | | | | | | |
V121I+Y93H | | | | | | | | |
L28I+R30P+P32F | | 78,000x | resistance likely | | 12 | 15 | | |
L28I+R30Q+P32L | | 34,666x | resistance likely | | 3 | 15 | | |
L28M+R30L+Q54H | | 0.3x | likely susceptible | | 18 | 15 | | |
L28M+R30Q+A92K | | 1310666 | resistance likely | | 49 | 15 | | |
L28M+R30Q+A92T | | 1.7x | likely susceptible | | 16 | 15 | | |
L28M+R30Q+Y93H | | 1,666,667x | resistance likely | | 5 | 15 | | |
L28M+R30Q+Y93S | | 667x | resistance likely | | 9 | 15 | | |
L28T+R30Q+Y93H | | 41,667x | resistance likely | | 2 | 15 | | |
L28V+R30Q+Y93H | | 2,766x | resistance likely | | 42 | 15 | | |
P29S+R30Q+Y93S | | 216,333x | resistance likely | | | | | |
R30H+P58S+Y93H | | 6,000x | resistance likely | | 22 | 15 | | |
R30Q+L31F+Y93H | | 51,666x | resistance likely | | | 15 | | |
R30Q+L31M+Y93H | | 20,333x | resistance likely | | 88 | 15 | | |
R30Q+Q54H+A92K | | 8667x | resistance likely | Yes | | 14 | | Clincal VF RAV (14) |
L31F+Q54H+Y93H | | 6,333x | resistance likely | | 161 | 15 | | |
L31F+Y93H+V121I | | | | | | | | |
L31F+Q54F+A92E | | | | | | | | |
L31I+A92V+Y93H | | 3,667x | resistance likely | | 15 | 15 | | |
L31I+P58S+Y93H | | 54,667x | resistance likely | | 16 | 15 | | |
L31M+A92V+Y93H | | 19,333x | resistance likely | | 22 | 15 | | |
L31M+P58A+Y93H | >1000 | 65000x | resistance likely | Yes | 7 | 8,15 | | Clinical VF RAV (8) |
L31M+P58G+Y93H | >5000 | 100000x | resistance likely | Yes | 17 | 8,15 | | Clinical VF RAV (8) |
L31M+P58L+Y93H | | 13,000x | resistance likely | | 12 | 15 | | |
L31M+P58S+Y93H | | 70,000x | resistance likely | | 10 | 15 | | |
L31M+Q54H+A92E | | 100x | resistance possible | | 33 | 15 | | |
L31M+Q54H+Y93H | | 4,233x | resistance likely | Yes | 88 | 14,15 | | Clincal VF RAV (14) |
L31M+Q54Y+Y93H | | 6466x | resistance likely | | 41 | 15 | | |
L31V+P58A+Y93H | | 204,000x | resistance likely | | 12 | 15 | | |
L31V+P58S+Y93H | | 140,333x | resistance likely | | 17 | 15 | | |
L31V+Q54H+Y93H | | 8,667x | resistance likely | | 31 | 15 | | |
L31V+Q54H+Y93H | 36.1 | 19000x | resistance likely | Yes | 189 | 4,8,14 | | Clincal VF RAV (14) |
L31V+Q54Y+Y93H | | 25,333x | resistance likely | | 4 | 15 | | |
L31V+Q62E+Y93H | | 67,333x | resistance likely | | 87 | 15 | | |
Q54H+A92V+Y93H | | | | | | | | |
Q54H+P58A+Q62E | | 0.7x | likely susceptible | | 176 | 15 | | |
Q54H+P58S+A92K | | 16,333x | resistance likely | | 15 | 15 | | |
Q54H+P58S+Y93H | | 200x | resistance likely | | 42 | 15 | | |
L28M+L31V+P58S+Y93N | | 1,666,667x | resistance likely | | 28 | 15 | | |
L28M+R30H+L31V+Y93H | | 1,666,667x | resistance likely | | 21 | 15 | | |
L28M+R30H+Q54H+Y93H | | 38,333x | resistance likely | | 20 | 15 | | |
L28M+R30Q+L31I+Y93H | | 194,333x | resistance likely | | 21 | 15 | | |
L28M+R30Q+L31V+Y93H | | 557,333x | resistance likely | Yes | | 14 | | Clincal VF RAV (14) |
L28M+R30Q+Q54H+A92T | | 0.7x | likely susceptible | | 46 | 15 | | |
R30Q+L31M+P58S+Y93H | | 44,000x | resistance likely | | 2.5 | 15 | | |
R30Q+L31M+Q54H+Y93H | | 4,666x | resistance likely | | 154 | 15 | | |
R30Q+L31V+P58S+Y93H | | 76,333x | resistance likely | | 9.7 | 15 | | |
L31IM+Q54H+Q62E+Y93H | | 9,333x | resistance likely | Yes | | 14 | | Clincal VF RAV (14) |
L31I+Q54H+P58S+Y93H | | 14,000x | resistance likely | | 95 | 15 | | |
L31M+Q54H+A92E+Y93H | | 113,333x | resistance likely | | 32 | 15 | | |
L31M+Q54H+A92V+Y93H | | 4,333x | resistance likely | | 12 | 15 | | |
L31M+Q54H+P58S+Y93H | | 17,667x | resistance likely | | 35 | 15 | | |
L31M+Q54H+Q62E+Y93H | | 9,333x | resistance likely | | 46 | 15 | | |
L31M+Q54Y+P58S+Y93H | | 50,000x | resistance likely | | 21 | 15 | | |
L31V+Q54H+P58S+Y93H | | 111333x | resistance likely | | 11 | 15 | | |
L31V+Q54H+Q62D+Y93H | | 31,333x | resistance likely | | 203 | 15 | | |
L31V+Q54H+Q62E+Y93H | | 31,667x | resistance likely | | 34 | 15 | | |
| | | | | | | | |
1. Zhou et al. (2015) JID 2015;213:206-15 |
2. Lontok et al. (2015) Hepatology in press |
3. EASL Guidelines 2016 |
4. Sarrazin C. 2016. Journal of hepatology 64: 486-504 |
5. FDA NDA Microbiology Virology Reviews_Daklinza_206843Orig1s000MicroR |
Elbasvir
Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments | SVR with any RAVs at position |
WT (1b_con1) | 0.003 | 1x | likely susceptible | | 2,3 | 0.009 in ref 1 | 99 - 100% (4) |
Q24K | | | | | | | |
Q24R | | | | | | | |
L28A | | | | | | | |
L28M | 0.006 | 2x | resistance possible | Yes | 2,3,5 | Clinical TE RAV (3,5) | 80% (5) |
L28T | | | | | 4 | | |
L28I | | | | | | | |
L28V | 0.004 | 1.3x | likely susceptible | | 5,4 | | |
P29S | | | | | | | |
P29del | | | | | | | |
R30G | | | | | 4 | | |
R30H | | | | | 4 | | 100% (5) |
R30K | | | | | | | |
R30L | | | | | | | |
R30P | | | | | 4 | | |
R30Q | 0.009 | 3x | resistance likely | Yes | 9,4 | Clincial VF RAV (5) | |
R30S | | | | | | | |
R30T | | | | | | | |
L31F | 0.05 | 15x | resistance likely | Yes | 2,1,3,4,5 | Clinical TE RAV (3,5) | |
L31I | | | | | 4 | | |
L31K | | | | | | | |
L31M | 0.02 | 7x | resistance likely | Yes | 2,1,3,4,6 | Clinical TE RAV (3) | 85% (5) |
L31T | | | | | 4 | | |
L31V | 0.04 | 13x | resistance likely | Yes | 1,4,2,5 | Clinical TE RAV (5), stable replicon=3.3x (5) | 100% (5) |
L31W | | | | | | | |
P32F | | | | | | | |
P32L | | | | | | | |
P32K | | | | | | | |
P32R | | | | | | | |
P32N | | | | | | | |
P32K | | | | | | | |
P32T | | | | | | | |
P32S | | | | | | | |
P32del | | | | | | | |
F37L | | | | | | | |
Q54H | | | | | | | |
Q54N | | | | | | | |
Q54L | | | | | | | |
Q54Y | | | | | | | |
P58A | | | | | | | |
P58D | | | | | | | 100% (4) |
P58L | | | | | | | |
P58Q | | | | | | | |
P58R | | | | | | | |
P58S | | | resistance possible | Yes | 5 | Clinical VF RAV (5) | |
P58T | | | | | | | |
Q62D | | | | | | | |
Q62E | 0.007 | 2.3x | likely susceptible | | 5 | | |
Q62A | | | | | | | |
Q62H | | | | | | | |
Q62N | | | | | | | |
Q62R | | | | | | | |
Q62S | | | | | | | |
A92E | | | | | | | |
A92V | | | | | | | |
A92K | | | | | | | |
A92P | | | | | | | |
A92T | | | | | | | |
A92V | | | | | | | 100% (4) |
Y93C | 0.005 | 1.7x | likely susceptible | | 5 | | |
Y93H | 0.2 | 67x | resistance likely | Yes | 1,3,5,6 | Clinical TE RAV (3,5) | 94% (5) |
Y93N | | | | | | | |
Y93F | | | | | | | |
Y93L | | | | | | | |
Y93R | | | | | | | |
Y93T | | | | | | | |
Y93S | | | | | | | 100% (5) |
V121I | 0.0005 | 0.2x | likely susceptible | | 2 | | |
D320E | | | | | | | |
L23F+L31F | | | | | | | |
Q24R+R30Q | | | | | | | |
L28I+R30Q | | | | | | | |
L28M+L31F | | | | | | | |
L28M+P32del | | | | | | | |
L28M+R30L | | | | | | | |
L28M+R30Q | | | | | | | |
L28M+R30Q | | | | | | | |
L28M+Y93H | | | | | | | |
L28V+L31F | | | | | | | |
L28V+R30Q | | | | | | | |
R30H+Y93H | | | | | | | |
R30L+L31M | | | | | | | |
R30Q+L31M | | | | | | | |
R30Q+L31F | | | | | | | |
R30Q+L31V | | | | | | | |
R30Q+Q54H | | | | | | | |
R30Q+A92K | | | | | | | |
R30Q+Y93H | | | | | | | |
R30Q+Y93S | | | | | | | |
L31F+A92E | | | | | | | |
L31F+P32del | | | | | | | |
L31F+P58L | | | | | | | |
L31F+Q54H | | | | | | | |
L31F+Y93H | | | | | | | |
L31IV+Y93H | | | | | | | |
L31I+A92V | | | | | | | |
L31I+Y93H | | | | | | | |
L31M+A92K | | | | | | | |
L31M+P58L | | | | | | | |
L31M+P58S | | | | | | | |
L31M+Q54H | | | | | | | |
L31M+Y93C | | | | | | | |
L31M+Y93H | | | | | | | |
L31M+Y93N | | | | | | | |
L31V+P32del | | | | | | | |
L31V+Y93H | | | | | | | |
L31V+Y93N | | | | | | | |
P32del+Y93H | | | | | | | |
F37L+Y93H | | | | | | | |
Q54H+Q62E | | | | | | | |
Q54H+A92E | | | | | | | |
Q54H+Y93H | | | | | | | |
Q54H+Y93S | | | | | | | |
Q54Y+Y93H | | | | | | | |
P58A+Y93H | | | | | | | |
P58L+Y93H | | | | | | | |
P58S+A92T | | | | | | | |
P58S+Y93H | | | | | | | |
Q62E+Y93H | 0.04 | 13.3x | resistance likely | | 5 | | |
A92T+Y93H | | | | | | | |
A92V+Y93H | | | | | | | |
V121I+Y93H | 0.6 | 200x | resistance likely | | 5 | | |
L28I+R30P+P32F | | | | | | | |
L28I+R30Q+P32L | | | | | | | |
L28M+R30L+Q54H | | | | | | | |
L28M+R30Q+A92K | | | | | | | |
L28M+R30Q+A92T | | | | | | | |
L28M+R30Q+Y93H | | | | | | | |
L28M+R30Q+Y93S | | | | | | | |
L28T+R30Q+Y93H | | | | | | | |
L28V+R30Q+Y93H | | | | | | | |
P29S+R30Q+Y93S | | | | | | | |
R30H+P58S+Y93H | | | | | | | |
R30Q+L31F+Y93H | | | | | | | |
R30Q+L31M+Y93H | | | | | | | |
R30Q+Q54H+A92K | | | | | | | |
L31F+Q54H+Y93H | | | | | | | |
L31F+Y93H+V121I | | 27 | resistance likely | | 5 | | |
L31F+Q54F+A92E | | | | | | | |
L31I+A92V+Y93H | | | | | | | |
L31I+P58S+Y93H | | | | | | | |
L31M+A92V+Y93H | | | | | | | |
L31M+P58A+Y93H | | | | | | | |
L31M+P58G+Y93H | | | | | | | |
L31M+P58L+Y93H | | | | | | | |
L31M+P58S+Y93H | | | | | | | |
L31M+Q54H+A92E | | | | | | | |
L31M+Q54H+Y93H | | | | | | | |
L31M+Q54Y+Y93H | | | | | | | |
L31V+P58A+Y93H | | | | | | | |
L31V+P58S+Y93H | | | | | | | |
L31V+Q54H+Y93H | | | | | | | |
L31V+Q54H+Y93H | | | | | | | |
L31V+Q54Y+Y93H | | | | | | | |
L31V+Q62E+Y93H | | | | | | | |
Q54H+A92V+Y93H | | | | | | | |
Q54H+P58A+Q62E | | | | | | | |
Q54H+P58S+A92K | | | | | | | |
Q54H+P58S+Y93H | | | | | | | |
L28M+L31V+P58S+Y93N | | | | | | | |
L28M+R30H+L31V+Y93H | | | | | | | |
L28M+R30H+Q54H+Y93H | | | | | | | |
L28M+R30Q+L31I+Y93H | | | | | | | |
L28M+R30Q+L31V+Y93H | | | | | | | |
L28M+R30Q+Q54H+A92T | | | | | | | |
R30Q+L31M+P58S+Y93H | | | | | | | |
R30Q+L31M+Q54H+Y93H | | | | | | | |
R30Q+L31V+P58S+Y93H | | | | | | | |
L31IM+Q54H+Q62E+Y93H | | | | | | | |
L31I+Q54H+P58S+Y93H | | | | | | | |
L31M+Q54H+A92E+Y93H | | | | | | | |
L31M+Q54H+A92V+Y93H | | | | | | | |
L31M+Q54H+P58S+Y93H | | | | | | | |
L31M+Q54H+Q62E+Y93H | | | | | | | |
L31M+Q54Y+P58S+Y93H | | | | | | | |
L31V+Q54H+P58S+Y93H | | | | | | | |
L31V+Q54H+Q62D+Y93H | | | | | | | |
L31V+Q54H+Q62E+Y93H | | | | | | | |
1. Zapatier Canadian Product label |
2. Zepatier US Product Label |
3. FDA Microbiology/Virology Reviews Zepatier_virology _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 |
Ledipasvir
Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
WT (1b_con1) | 0.004 | 1x | likely susceptible | | 1,4,6 | |
Q24K | | <2.5x | likely susceptible | | 11 | |
Q24R | | | | | | |
L28A | | | | | | |
L28M | | <2.5x | resistance possible | Yes | 4,9,11 | Clinical VF RAV (4,9), BL RAV asso VF |
L28T | | | | | | |
L28I | | | | | | |
L28V | | <2.5x | likely susceptible | | 11 | |
P29S | | | | | | |
P29del | | | | | | |
R30G | | | | | | |
R30H | | <2.5x | likely susceptible | | 11 | |
R30K | | <2.5x | likely susceptible | | 11 | |
R30L | | <2.5x | likely susceptible | | 11 | |
R30P | | | | | | |
R30Q | | <2.5x | likely susceptible | | 11 | |
R30S | | <2.5x | likely susceptible | | 11 | |
R30T | | <2.5x | likely susceptible | | 11 | |
L31F | | 2x | likely susceptible | | 6,3 | |
L31I | | 10-50x | resistance possible | Yes | 5,4, 6, 7,3 | clinical TE RAV (4,8) |
L31K | | | | | | |
L31M | | 3x | resistance possible | Yes | 10,5, 4, 6,3 | clinical TE RAV (4,8) |
L31T | | | | | | |
L31V | | 10-50x | resistance possible | Yes | 5, 4,6,3,9 | clinical TE RAV (4,8,9) |
L31W | | | | | | |
P32F | | | | | | |
P32L | | | | | | |
P32K | | | | | | |
P32R | | | | | | |
P32N | | | | | | |
P32K | | | | | | |
P32T | | 2.5-10x | likely susceptible | | 5,3 | |
P32S | | | | | | |
P32del | | | | | | |
F37L | | | | | | |
Q54H | | <2.5x | likely susceptible | | 11 | |
Q54N | | | | | | |
Q54L | | | | | | |
Q54Y | | | | | | |
P58A | | | | | | |
P58D | | 100-1000x | resistance likely | | 5, 3,11 | |
P58L | | | | | | |
P58Q | | <2.5x | likely susceptible | | 11 | |
P58R | | <2.5x | likely susceptible | | 11 | |
P58S | | <2.5x | likely susceptible | | 11 | |
P58T | | <2.5x | likely susceptible | | 11 | |
Q62D | | | | | | |
Q62E | | | | | | |
Q62A | | | | | | |
Q62H | | | | | | |
Q62N | | | | | | |
Q62R | | | | | | |
Q62S | | | | | | |
A92E | | <2.5x | likely susceptible | | 11 | |
A92V | | | | | | |
A92K | | >1000x | resistance likely | | 5,3,11 | |
A92P | | | | | | |
A92T | | <2.5x | resistance possible | Yes | 4,9 | Clinical VF RAV (4,9), BL RAV asso VF |
A92V | | <2.5x | likely susceptible | | 11 | |
Y93C | | | resistance possible | Yes | 3,2 | clinical TE RAV (2) |
Y93H | 5.3 | 1325x | resistance likely | Yes | 1,4,5,6,3,2,10,11 | clinical TE RAV (2,4,8) |
Y93N | | >100x | resistance likely | | 11,3 | |
Y93F | | <2.5x | likely susceptible | | 11 | |
Y93L | | <2.5x | likely susceptible | | 11 | |
Y93R | | | | | | |
Y93T | | | | | | |
Y93S | | <100x | resistance possible | | 11,3 | |
V121I | | | | | | |
D320E | | | | | | |
L23F+L31F | | | | | | |
Q24R+R30Q | | <2.5x | likely susceptible | | 11 | |
L28I+R30Q | | | | | | |
L28M+L31F | | | | | | |
L28M+P32del | | | | | | |
L28M+R30L | | | | | | |
L28M+R30Q | | | | | | |
L28M+R30Q | | | | | | |
L28M+Y93H | | >100x | resistance likely | | 11 | |
L28V+L31F | | | | | | |
L28V+R30Q | | | | | | |
R30H+Y93H | | | | | | |
R30L+L31M | | | | | | |
R30Q+L31M | | | | | | |
R30Q+L31F | | | | | | |
R30Q+L31V | | | | | | |
R30Q+Q54H | | | | | | |
R30Q+A92K | | | | | | |
R30Q+Y93H | | >100x | resistance likely | | 11 | |
R30Q+Y93S | | | | | | |
L31F+A92E | | | | | | |
L31F+P32del | | | | | | |
L31F+P58L | | | | | | |
L31F+Q54H | | | | | | |
L31F+Y93H | | | | | | |
L31IV+Y93H | | | | | | |
L31I+A92V | | | | | | |
L31I+Y93H | | >100x | resistance likely | | 11 | |
L31M+A92K | | | | | | |
L31M+P58L | | | | | | |
L31M+P58S | | | | | | |
L31M+Q54H | | | | | | |
L31M+Y93C | | >100x | resistance likely | | 11 | |
L31M+Y93H | | 20270x | resistance likely | | 10 | |
L31M+Y93N | | | | | | |
L31V+P32del | | | | | | |
L31V+Y93H | | >100x | resistance likely | | 11 | |
L31V+Y93N | | >100x | resistance likely | | 11 | |
P32del+Y93H | | | | | | |
F37L+Y93H | | | | | | |
Q54H+Q62E | | | | | | |
Q54H+A92E | | | | | | |
Q54H+Y93H | | | | | | |
Q54H+Y93S | | | | | | |
Q54Y+Y93H | | | | | | |
P58A+Y93H | | | | | | |
P58L+Y93H | | | | | | |
P58S+A92T | | | | | | |
P58S+Y93H | | | | | | |
Q62E+Y93H | | | | | | |
A92T+Y93H | | | | | | |
A92V+Y93H | | | | | | |
V121I+Y93H | | | | | | |
L28I+R30P+P32F | | | | | | |
L28I+R30Q+P32L | | | | | | |
L28M+R30L+Q54H | | | | | | |
L28M+R30Q+A92K | | | | | | |
L28M+R30Q+A92T | | | | | | |
L28M+R30Q+Y93H | | | | | | |
L28M+R30Q+Y93S | | | | | | |
L28T+R30Q+Y93H | | | | | | |
L28V+R30Q+Y93H | | | | | | |
P29S+R30Q+Y93S | | | | | | |
R30H+P58S+Y93H | | | | | | |
R30Q+L31F+Y93H | | | | | | |
R30Q+L31M+Y93H | | | | | | |
R30Q+Q54H+A92K | | | | | | |
L31F+Q54H+Y93H | | | | | | |
L31F+Y93H+V121I | | | | | | |
L31F+Q54F+A92E | | | | | | |
L31I+A92V+Y93H | | | | | | |
L31I+P58S+Y93H | | | | | | |
L31M+A92V+Y93H | | | | | | |
L31M+P58A+Y93H | | | | | | |
L31M+P58G+Y93H | | | | | | |
L31M+P58L+Y93H | | | | | | |
L31M+P58S+Y93H | | | | | | |
L31M+Q54H+A92E | | | | | | |
L31M+Q54H+Y93H | | | | | | |
L31M+Q54Y+Y93H | | | | | | |
L31V+P58A+Y93H | | | | | | |
L31V+P58S+Y93H | | | | | | |
L31V+Q54H+Y93H | | | | | | |
L31V+Q54H+Y93H | | | | | | |
L31V+Q54Y+Y93H | | | | | | |
L31V+Q62E+Y93H | | | | | | |
Q54H+A92V+Y93H | | | | | | |
Q54H+P58A+Q62E | | | | | | |
Q54H+P58S+A92K | | | | | | |
Q54H+P58S+Y93H | | | | | | |
L28M+L31V+P58S+Y93N | | | | | | |
L28M+R30H+L31V+Y93H | | | | | | |
L28M+R30H+Q54H+Y93H | | | | | | |
L28M+R30Q+L31I+Y93H | | | | | | |
L28M+R30Q+L31V+Y93H | | | | | | |
L28M+R30Q+Q54H+A92T | | | | | | |
R30Q+L31M+P58S+Y93H | | | | | | |
R30Q+L31M+Q54H+Y93H | | | | | | |
R30Q+L31V+P58S+Y93H | | | | | | |
L31IM+Q54H+Q62E+Y93H | | | | | | |
L31I+Q54H+P58S+Y93H | | | | | | |
L31M+Q54H+A92E+Y93H | | | | | | |
L31M+Q54H+A92V+Y93H | | | | | | |
L31M+Q54H+P58S+Y93H | | | | | | |
L31M+Q54H+Q62E+Y93H | | | | | | |
L31M+Q54Y+P58S+Y93H | | | | | | |
L31V+Q54H+P58S+Y93H | | | | | | |
L31V+Q54H+Q62D+Y93H | | | | | | |
L31V+Q54H+Q62E+Y93H | | | | | | |
1. Zhou et al. (2015) JID 2015;213:206-15 |
2. Harvoni US Product Label (Nov 2015) |
3. Verrmhren et al. Www.natap.org/2017/AASLD_156.htm |
4. Camus G, J Viral Hepat. 2017;00:1–10.
https://doi.org/10.1111/jvh.12795 |
Ombitasvir
Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
WT (1b_con1) | 0.005 | 1x | likely susceptible | | 4,8 | |
Q24K | | | | | | |
Q24R | | | | | | |
L28A | | | | | | |
L28M | 0.0013 | 2x | resistance possible | Yes | 1,7,9,12 | clinical VF RAV (7,9) |
L28T | 0.522 | 661x | resistance likely | | 1, 6, 4,9,12 | |
L28I | | | | | | |
L28V | | | | | | |
P29S | | | | | | |
P29del | 285.3 | 361139x | resistance likely | | 9, 12 | |
R30G | | <10x | likely susceptible | | 8 | |
R30H | | <10x | likely susceptible | | 8 | |
R30K | | | | | | |
R30L | | | | | | |
R30P | | <10x | likely susceptible | | 8 | |
R30Q | 0.0003 | 0.4x | resistance possible | Yes | 1,8, 7,9,12 | clinical VF RAV(7,9) |
R30S | | | | | | |
R30T | | | | | | |
L31F | 0.0076 | 10x | resistance possible | Yes | 1, 4, 7, 8,9,11,12 | clinical TE RAV (7) |
L31I | | 2x | likely susceptible | | 11,8 | |
L31K | | | | | | |
L31M | 0.0007 | 0.9x | resistance possible | Yes | 1, 8, 7,12,13 | clinical VF RAV(1) |
L31T | | <10x | likely susceptible | | 8 | |
L31V | 0.0066 | 8X | resistance possible | Yes | 1, 4, 7, 8,9,12 | clinical TE RAV (7,9) |
L31W | | | | | | |
P32F | | | | | | |
P32L | | | | | | |
P32K | | | | | | |
P32R | | | | | | |
P32N | | | | | | |
P32K | | | | | | |
P32T | | >2.5x | | | 10 | |
P32S | | | | | | |
P32del | | | | | 8 | |
F37L | | | | | | |
Q54H | | | | | 7 | impact equivocal (7) |
Q54N | | | | | 7 | impact equivocal (7) |
Q54L | | | | | | |
Q54Y | | | resistance possible | Yes | 4,11 | clinical TE RAV (4,11) |
P58A | | | | | 9 | |
P58D | | >2.5x | | | 10 | |
P58L | | | | | | |
P58Q | | | | | | |
P58R | | | | | | |
P58S | | 0.8x | resistance possible | Yes | 7,9,12 | clinical TE RAV (2,7,9) |
P58T | 0.3 | 0.4x | likely susceptible | | 12 | |
Q62D | | | | | 7 | BL impact equivocal (7) |
Q62E | | | | | | |
Q62A | | | | | | |
Q62H | | | | | | |
Q62N | | | | | | |
Q62R | | | | | | |
Q62S | | | | | | |
A92E | | 0.7x | likely susceptible | | 7,9 | |
A92V | | | | | | |
A92K | | | | | | |
A92P | | | | | | |
A92T | | | | | 7 | impact equivocal (7) |
A92V | | | | | | |
Y93C | | | | | | |
Y93H | 0.06 | 77x | resistance likely | Yes | 1, 3, 5, 7, 8,9,11,12,13 | clinical VF RAV (5,4,7,9,11) |
Y93N | | 202x | resistance likely | | 9 | |
Y93F | | | | | | |
Y93L | | | | | | |
Y93R | | | | | | |
Y93T | | | | | | |
Y93S | | 12x | resistance possible | Yes | 7,9 | Clinial VF RAV (9) |
V121I | | | | | | |
D320E | | | | | | |
L23F+L31F | | | | | | |
Q24R+R30Q | | | | | | |
L28I+R30Q | | | | | | |
L28M+L31F | | 569X | resistance likely | | 1 | |
L28M+P32del | | | | | | |
L28M+R30L | | | | | | |
L28M+R30Q | | | | | | |
L28M+R30Q | | 0.5x | resistance possible | Yes | 7 | clinical TE RAV(7) |
L28M+Y93H | 0.328 | 415x | resistance likely | | 1, 6, 7,12 | |
L28V+L31F | | 2170X | resistance likely | | 1 | |
L28V+R30Q | | | | | | |
R30H+Y93H | | | | | | |
R30L+L31M | | | | | | |
R30Q+L31M | | | | | | |
R30Q+L31F | | | | | | |
R30Q+L31V | | | | | | |
R30Q+Q54H | | | | | | |
R30Q+A92K | | | | | | |
R30Q+Y93H | 0.224 | 284x | resistance likely | | 1, 7, 8,12 | |
R30Q+Y93S | | | | | | |
L31F+A92E | | 1022x | resistance likely | | 7 | |
L31F+P32del | | | | | | |
L31F+P58L | | 78x | resistance possible | | 1 | |
L31F+Q54H | | | | | | |
L31F+Y93H | 0.328, 8.1 | 415,1027x | resistance likely | | 1,6,12 | |
L31IV+Y93H | | | | | | |
L31I+A92V | | | | | | |
L31I+Y93H | | | | | | |
L31M+A92K | | | | | | |
L31M+P58L | | | | | | |
L31M+P58S | | | | | | |
L31M+Q54H | | | | | | |
L31M+Y93C | | | | | | |
L31M+Y93H | 0.112 | 142x | resistance likely | | 12,6, 7, 8 | |
L31M+Y93N | | | | | | |
L31V+P32del | | | | | | |
L31V+Y93H | 9.7 | 12328x | resistance likely | | 12,1, 7 | |
L31V+Y93N | | | | | | |
P32del+Y93H | | | | | | |
F37L+Y93H | | | | | | |
Q54H+Q62E | | | | | | |
Q54H+A92E | | | | | | |
Q54H+Y93H | | | | | | |
Q54H+Y93S | | | | | | |
Q54Y+Y93H | | | | | | |
P58A+Y93H | 0.967 | 1226x | resistance likely | | 1 | |
P58L+Y93H | 0.107 | 135x | resistance likely | | 1 | |
P58S+A92T | | | | | | |
P58S+Y93H | 1.1 | 1401x | resistance likely | | 7,12 | |
Q62E+Y93H | | | | | | |
A92T+Y93H | | | | | | |
A92V+Y93H | | | | | | |
V121I+Y93H | | | | | | |
L28I+R30P+P32F | | | | | | |
L28I+R30Q+P32L | | | | | | |
L28M+R30L+Q54H | | | | | | |
L28M+R30Q+A92K | | | | | | |
L28M+R30Q+A92T | | | | | | |
L28M+R30Q+Y93H | | 981x | resistance likely | | 7 | |
L28M+R30Q+Y93S | | | | | | |
L28T+R30Q+Y93H | | | | | | |
L28V+R30Q+Y93H | | | | | | |
P29S+R30Q+Y93S | | | | | | |
R30H+P58S+Y93H | | | | | | |
R30Q+L31F+Y93H | | | | | | |
R30Q+L31M+Y93H | | | | | | |
R30Q+Q54H+A92K | | | | | | |
L31F+Q54H+Y93H | | | | | | |
L31F+Y93H+V121I | | | | | | |
L31F+Q54F+A92E | | | | | | |
L31I+A92V+Y93H | | | | | | |
L31I+P58S+Y93H | | | | | | |
L31M+A92V+Y93H | | | | | | |
L31M+P58A+Y93H | | | | | | |
L31M+P58G+Y93H | | | | | | |
L31M+P58L+Y93H | | | | | | |
L31M+P58S+Y93H | | | | | | |
L31M+Q54H+A92E | | | | | | |
L31M+Q54H+Y93H | | | | | | |
L31M+Q54Y+Y93H | | | | | | |
L31V+P58A+Y93H | | | | | | |
L31V+P58S+Y93H | | | | | | |
L31V+Q54H+Y93H | | | | | | |
L31V+Q54H+Y93H | | | | | | |
L31V+Q54Y+Y93H | | | | | | |
L31V+Q62E+Y93H | | | | | | |
Q54H+A92V+Y93H | | | | | | |
Q54H+P58A+Q62E | | | | | | |
Q54H+P58S+A92K | | | | | | |
Q54H+P58S+Y93H | | | | | | |
L28M+L31V+P58S+Y93N | | | | | | |
L28M+R30H+L31V+Y93H | | | | | | |
L28M+R30H+Q54H+Y93H | | | | | | |
L28M+R30Q+L31I+Y93H | | | | | | |
L28M+R30Q+L31V+Y93H | | | | | | |
L28M+R30Q+Q54H+A92T | | | | | | |
R30Q+L31M+P58S+Y93H | | | | | | |
R30Q+L31M+Q54H+Y93H | | | | | | |
R30Q+L31V+P58S+Y93H | | | | | | |
L31IM+Q54H+Q62E+Y93H | | | | | | |
L31I+Q54H+P58S+Y93H | | | | | | |
L31M+Q54H+A92E+Y93H | | | | | | |
L31M+Q54H+A92V+Y93H | | | | | | |
L31M+Q54H+P58S+Y93H | | | | | | |
L31M+Q54H+Q62E+Y93H | | | | | | |
L31M+Q54Y+P58S+Y93H | | | | | | |
L31V+Q54H+P58S+Y93H | | | | | | |
L31V+Q54H+Q62D+Y93H | | | | | | |
L31V+Q54H+Q62E+Y93H | | | | | | |
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1. Schnell G. et al. (2015) AAC 59:68-7 – 6815 |
2. Lontok et al. (2015) Hepatology 62.5: 1623-1632. |
3. Technivie US Product Label Jan 28, 2016 |
4. Stirnimann G (2014) Expert Opinion Pharmacother. 15(17):2609 – 2622 |
5. Technivie Canadian Product Monograph Nov 24, 2015 |
6. FDA NDA Microbiology Virology Reviews Technive_207931Orig1s000MedR |
Pibrentasvir
Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Replicative Fitness (3) | Reference | Comments |
WT (1b_con1) | 0.0043 | 1x | likely susceptible | | 100 | 1,11,3 | 0.0014 - 0.0043, n=8 clincial isolates |
Q24K | | | | | | | |
Q24R | | | | | | | |
L28A | | | | | | | |
L28M | 0.0018 | 1x | resistance possible | Yes | 114 | 3 | Clinical VF RAV (3) |
L28T | 0.0017 | 0.9x | likely susceptible | | 17 | 1,3 | |
L28I | | | | | | | |
L28V | | | | | | | |
P29S | | | | | | | |
P29del | 0.0193 | 10x | resistance possible | | 5.6 | 3 | |
R30G | | | | | | | |
R30H | | | | | | | |
R30K | | | | | | | |
R30L | | | | | | | |
R30P | | | | | | | |
R30Q | 0.00088 | 0.5x | resistance possible | Yes | | 3 | Clincal VF RAS, 2% (3) |
R30S | | | | | | | |
R30T | | | | | | | |
L31F | 0.0023 | 1.2x | likely susceptible | | 127 | 3 | |
L31I | | | | | | | |
L31K | | | resistance possible | Yes | | | Clincal VF RAS, 2% (3) |
L31M | 0.0031 | 1.4-1.5x | likely susceptible | | 119 | 2,3,4 | |
L31T | | | | | | | |
L31V | 0.0015 | 0.8x | likely susceptible | | 86 | 3 | |
L31W | | | | | | | |
P32F | | | | | | | |
P32L | | | | | | | |
P32K | | | resistance possible | Yes | | 3 | Clincial TE RAS (3) |
P32R | | | resistance possible | Yes | | 3 | Clincal VF RAS, 4% (3) |
P32N | | | resistance possible | Yes | | 3 | Clinical VF RAS, 18% (3) |
P32K | | | resistance possible | Yes | | 3 | Clincial VF RAS, 70% (3) |
P32T | | | resistance possible | Yes | | 3 | Clincal VF RAS, 8% (3) |
P32S | | | | | | | |
P32del | 1.968 | 1036x | resistance likely | Yes | | 3 | Clinical VF RAV (3) indicated as P32- |
F37L | | | | | | | |
Q54H | 0.0021 | 1.1x | likely susceptible | | 120 | 3 | |
Q54N | | | | | | | |
Q54L | | | | | | | |
Q54Y | 0.0023 | 1.2x | likely susceptible | | 112 | 3 | |
P58A | | | | | | | |
P58D | | | | | | | |
P58L | | | | | | | |
P58Q | | | | | | | |
P58R | | | | | | | |
P58S | 0.0028 | 1.3x | likely susceptible | | 80 | 2,3 | |
P58T | | | | | | | |
Q62D | | | | | | | |
Q62E | | | | | | | |
Q62A | | | | | | | |
Q62H | | | | | | | |
Q62N | | | | | | | |
Q62R | | | | | | | |
Q62S | | | | | | | |
A92E | 0.00092 | 0.5x | likely susceptible | | 29 | 3 | |
A92V | | | | | | | |
A92K | | | | | | | |
A92P | | | | | | | |
A92T | | | | | | | |
A92V | 0.00086 | 0.5x | likely susceptible | | 54 | 3 | |
Y93C | | | | | | | |
Y93H | 0.0011 | 0.6x | likely susceptible | | 73 | 1,2,3,4 | |
Y93N | 0.0012 | 0.6x | likely susceptible | | 52 | 1,3 | |
Y93F | | | | | | | |
Y93L | | | | | | | |
Y93R | | | | | | | |
Y93T | | | | | | | |
Y93S | 0.00074 | 0.4x | likely susceptible | | 23 | 3 | |
V121I | | | | | | | |
D320E | | | | | | | |
L23F+L31F | | | | | | | |
Q24R+R30Q | | | | | | | |
L28I+R30Q | | | | | | | |
L28M+L31F | | | | | | | |
L28M+P32del | 12.02 | 6326x | resistance likely | | | 3 | |
L28M+R30L | | | | | | | |
L28M+R30Q | 0.00079 | 0.4x | likely susceptible | | 28 | 3 | |
L28M+R30Q | 0.00079 | 0.4x | | | | 3 | |
L28M+Y93H | 0.0022 | 1.2x | likely susceptible | | 104 | 3 | |
L28V+L31F | | | | | | | |
L28V+R30Q | | | | | | | |
R30H+Y93H | | | | | | | |
R30L+L31M | | | | | | | |
R30Q+L31M | | | | | | | |
R30Q+L31F | | | | | | | |
R30Q+L31V | | | | | | | |
R30Q+Q54H | | | | | | | |
R30Q+A92K | | | | | | | |
R30Q+Y93H | 0.0023 | 1.2x | likely susceptible | | 60 | 3 | |
R30Q+Y93S | | | | | | | |
L31F+A92E | 0.0012 | 0.6x | likely susceptible | | 36 | 3 | |
L31F+P32del | | | | | | | |
L31F+P58L | | | | | | | |
L31F+Q54H | 0.0045 | 2.4x | likely susceptible | | 99 | 3 | |
L31F+Y93H | 0.0028 | 1.5x | likely susceptible | | 35 | 3 | |
L31IV+Y93H | | | | | | | |
L31I+A92V | | | | | | | |
L31I+Y93H | | | | | | | |
L31M+A92K | | | | | | | |
L31M+P58L | | | | | | | |
L31M+P58S | | | | | | | |
L31M+Q54H | | | | | | | |
L31M+Y93C | | | | | | | |
L31M+Y93H | 0.0013 | 0.7x | likely susceptible | | 11 | 1,3,4 | |
L31M+Y93N | | | | | | | |
L31V+P32del | | | | | | | |
L31V+Y93H | 0.0017 | 0.9x | likely susceptible | | 24 | 1,3 | |
L31V+Y93N | | | | | | | |
P32del+Y93H | | | | | | | |
F37L+Y93H | | | | | | | |
Q54H+Q62E | | | | | | | |
Q54H+A92E | 0.0017 | 0.9x | likely susceptible | | 62 | 3 | |
Q54H+Y93H | 0.0017 | 0.9x | likely susceptible | | 35 | 3 | |
Q54H+Y93S | | | | | | | |
Q54Y+Y93H | 0.002 | 1x | likely susceptible | | 34 | 3 | |
P58A+Y93H | | | | | | | |
P58L+Y93H | | | | | | | |
P58S+A92T | | | | | | | |
P58S+Y93H | 0.0015 | 0.8x | likely susceptible | | 34 | 1,3 | |
Q62E+Y93H | | | | | | | |
A92T+Y93H | | | | | | | |
A92V+Y93H | 0.00068 | 0.4x | likely susceptible | | 2.5 | 3 | |
V121I+Y93H | | | | | | | |
L28I+R30P+P32F | | | | | | | |
L28I+R30Q+P32L | | | | | | | |
L28M+R30L+Q54H | | | | | | | |
L28M+R30Q+A92K | | | | | | | |
L28M+R30Q+A92T | | | | | | | |
L28M+R30Q+Y93H | 0.001 | 0.5x | likely susceptible | | 28 | 3 | |
L28M+R30Q+Y93S | | | | | | | |
L28T+R30Q+Y93H | | | | | | | |
L28V+R30Q+Y93H | | | | | | | |
P29S+R30Q+Y93S | | | | | | | |
R30H+P58S+Y93H | | | | | | | |
R30Q+L31F+Y93H | | | | | | | |
R30Q+L31M+Y93H | | | | | | | |
R30Q+Q54H+A92K | | | | | | | |
L31F+Q54H+Y93H | | | | | | | |
L31F+Y93H+V121I | | | | | | | |
L31F+Q54F+A92E | 0.0032 | 1.7x | likely susceptible | | 70 | 3 | |
L31I+A92V+Y93H | | | | | | | |
L31I+P58S+Y93H | | | | | | | |
L31M+A92V+Y93H | | | | | | | |
L31M+P58A+Y93H | | | | | | | |
L31M+P58G+Y93H | | | | | | | |
L31M+P58L+Y93H | | | | | | | |
L31M+P58S+Y93H | | | | | | | |
L31M+Q54H+A92E | | | | | | | |
L31M+Q54H+Y93H | | | | | | | |
L31M+Q54Y+Y93H | | | | | | | |
L31V+P58A+Y93H | | | | | | | |
L31V+P58S+Y93H | | | | | | | |
L31V+Q54H+Y93H | | | | | | | |
L31V+Q54H+Y93H | | | | | | | |
L31V+Q54Y+Y93H | | | | | | | |
L31V+Q62E+Y93H | | | | | | | |
Q54H+A92V+Y93H | 0.0018 | 1x | likely susceptible | | 1.4 | 3 | |
Q54H+P58A+Q62E | | | | | | | |
Q54H+P58S+A92K | | | | | | | |
Q54H+P58S+Y93H | | | | | | | |
L28M+L31V+P58S+Y93N | | | | | | | |
L28M+R30H+L31V+Y93H | | | | | | | |
L28M+R30H+Q54H+Y93H | | | | | | | |
L28M+R30Q+L31I+Y93H | | | | | | | |
L28M+R30Q+L31V+Y93H | | | | | | | |
L28M+R30Q+Q54H+A92T | | | | | | | |
R30Q+L31M+P58S+Y93H | | | | | | | |
R30Q+L31M+Q54H+Y93H | | | | | | | |
R30Q+L31V+P58S+Y93H | | | | | | | |
L31IM+Q54H+Q62E+Y93H | | | | | | | |
L31I+Q54H+P58S+Y93H | | | | | | | |
L31M+Q54H+A92E+Y93H | | | | | | | |
L31M+Q54H+A92V+Y93H | | | | | | | |
L31M+Q54H+P58S+Y93H | | | | | | | |
L31M+Q54H+Q62E+Y93H | | | | | | | |
L31M+Q54Y+P58S+Y93H | | | | | | | |
L31V+Q54H+P58S+Y93H | | | | | | | |
L31V+Q54H+Q62D+Y93H | | | | | | | |
L31V+Q54H+Q62E+Y93H | | | | | | | |
1. Ng TI, et al. 2017. Antimicrobial agents and chemotherapy 61: e02558-16 https://doi.org/10.1128/ AAC.02558-16. |
2. FDA Microbiology Review https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209394Orig1s000MicroR.pdf |
Velpatasvir
Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
WT (1b_con1) | 0.015 | 1 | likely susceptible | | 1,2,5 | |
Q24K | | 2.5 - 100x | resistance possible | | 4,5,6 | VEL RAS (6) |
Q24R | | | | | | |
L28A | | | | | | |
L28M | | 0.7x | likely susceptible | | 8 | |
L28T | | | | | | |
L28I | | | | | | |
L28V | | <2.5x | likely susceptible | | 8 | |
P29S | | | | | | |
P29del | | | | | | |
R30G | | | | | | |
R30H | | <2.5x | likely susceptible | | 8 | |
R30K | | <2.5x | likely susceptible | | 8 | |
R30L | | <2.5x | likely susceptible | | 8 | |
R30P | | | | | | |
R30Q | | <2.5x | likely susceptible | | 8 | |
R30S | | <2.5x | likely susceptible | | 8 | |
R30T | | <2.5x | likely susceptible | | 8 | |
L31F | | 0.7x | likely susceptible | | 4,5,6 | VEL RAS (6) |
L31I | | 3.8x | resistance possible | | 4,5 | |
L31K | | | | | | |
L31M | 0.008 | 1.7x | resistance possible | Yes | 1,3,4,7,8 | Clincal TE RAV (3) |
L31T | | | | | | |
L31V | 0.008 | 2x | resistance possible | Yes | 3,1,8 | Clincal TE RAV (3,8) |
L31W | | | | | | |
P32F | | | | | | |
P32L | | <2.5x | likely susceptible | | 8 | |
P32K | | | | | | |
P32R | | | | | | |
P32N | | | | | | |
P32K | | | | | | |
P32T | | | | | | |
P32S | | | | | | |
P32del | | | | | | |
F37L | | | | | | |
Q54H | | 1x | likely susceptible | | 8 | |
Q54N | | | | | | |
Q54L | | | | | | |
Q54Y | | | | | | |
P58A | | | | | | |
P58D | | <2.5x | likely susceptible | | 8 | |
P58L | | | | | | |
P58Q | | <2.5x | likely susceptible | | 8 | |
P58R | | <2.5x | likely susceptible | | 8,4 | |
P58S | | <2.5x | likely susceptible | | 8 | |
P58T | | 2.5 - 100x | resistance possible | | 4,5,6 | VEL RAS (6) |
Q62D | | | | | | |
Q62E | | | | | | |
Q62A | | | | | | |
Q62H | | | | | | |
Q62N | | | | | | |
Q62R | | | | | | |
Q62S | | | | | | |
A92E | | <2.5x | likely susceptible | | 8 | |
A92V | | | | | | |
A92K | | >100x | resistance likely | | 4,5,6 | VEL RAS (6) |
A92P | | <2.5x | likely susceptible | | 8 | |
A92T | | <2.5x | likely susceptible | | 8 | |
A92V | | <2.5x | likely susceptible | | 8 | |
Y93C | | 0.2x | resistance possible | Yes | 3,8 | Clincal TE RAV (3) |
Y93H | 0.011 | 3x | resistance likely | Yes | 3,1,5,4,6,7 | Clincal TE RAV (3) |
Y93N | | 3x | resistance likely | Yes | 3,5,6 | Clincal TE RAV (3) |
Y93F | | <2.5x | likely susceptible | | 8 | |
Y93L | | <2.5x | likely susceptible | | 8 | |
Y93R | | >2.5 - 100x | resistance possible | | 6 | VEL RAS (6) |
Y93T | | 2.5 - 100x | resistance possible | | 4,5,6 | |
Y93S | | 0.6x | resistance possible | Yes | 3,8 | Clincal TE RAV (3) |
V121I | | | | | | |
D320E | | | | | | |
L23F+L31F | | | | | | |
Q24R+R30Q | | <2.5x | likely susceptible | | 8 | |
L28I+R30Q | | | | | | |
L28M+L31F | | | | | | |
L28M+P32del | | | | | | |
L28M+R30L | | | | | | |
L28M+R30Q | | | | | | |
L28M+R30Q | | | | | | |
L28M+Y93H | | 5x | resistance possible | | 8 | |
L28V+L31F | | | | | | |
L28V+R30Q | | | | | | |
R30H+Y93H | | | | | | |
R30L+L31M | | | | | | |
R30Q+L31M | | <2.5x | likely susceptible | | 8 | |
R30Q+L31F | | | | | | |
R30Q+L31V | | <2.5x | likely susceptible | | 8 | |
R30Q+Q54H | | | | | | |
R30Q+A92K | | | | | | |
R30Q+Y93H | | <2.5x | likely susceptible | | 8 | |
R30Q+Y93S | | | | | | |
L31F+A92E | | | | | | |
L31F+P32del | | | | | | |
L31F+P58L | | | | | | |
L31F+Q54H | | | | | | |
L31F+Y93H | | 27 | resistance likely | | 8 | |
L31IV+Y93H | | | | | | |
L31I+A92V | | | | | | |
L31I+Y93H | | | | | | |
L31M+A92K | | | | | | |
L31M+P58L | | | | | | |
L31M+P58S | | | | | | |
L31M+Q54H | | | | | | |
L31M+Y93C | | | | | | |
L31M+Y93H | | 44x | resistance likely | | 4,7,8 | |
L31M+Y93N | | >100x | resistance likely | | 8 | |
L31V+P32del | | | | | | |
L31V+Y93H | | 986x | resistance likely | | 2,8 | |
L31V+Y93N | | >100x | resistance likely | | 8 | |
P32del+Y93H | | | | | | |
F37L+Y93H | | | | | | |
Q54H+Q62E | | | | | | |
Q54H+A92E | | | | | | |
Q54H+Y93H | | | | | | |
Q54H+Y93S | | | | | | |
Q54Y+Y93H | | | | | | |
P58A+Y93H | | | | | | |
P58L+Y93H | | | | | | |
P58S+A92T | | | | | | |
P58S+Y93H | | | | | | |
Q62E+Y93H | | | | | | |
A92T+Y93H | | | | | | |
A92V+Y93H | | | | | | |
V121I+Y93H | | | | | | |
L28I+R30P+P32F | | | | | | |
L28I+R30Q+P32L | | | | | | |
L28M+R30L+Q54H | | | | | | |
L28M+R30Q+A92K | | | | | | |
L28M+R30Q+A92T | | | | | | |
L28M+R30Q+Y93H | | | | | | |
L28M+R30Q+Y93S | | | | | | |
L28T+R30Q+Y93H | | | | | | |
L28V+R30Q+Y93H | | | | | | |
P29S+R30Q+Y93S | | | | | | |
R30H+P58S+Y93H | | | | | | |
R30Q+L31F+Y93H | | | | | | |
R30Q+L31M+Y93H | | | | | | |
R30Q+Q54H+A92K | | | | | | |
L31F+Q54H+Y93H | | | | | | |
L31F+Y93H+V121I | | | | | | |
L31F+Q54F+A92E | | | | | | |
L31I+A92V+Y93H | | | | | | |
L31I+P58S+Y93H | | | | | | |
L31M+A92V+Y93H | | | | | | |
L31M+P58A+Y93H | | | | | | |
L31M+P58G+Y93H | | | | | | |
L31M+P58L+Y93H | | | | | | |
L31M+P58S+Y93H | | | | | | |
L31M+Q54H+A92E | | | | | | |
L31M+Q54H+Y93H | | | | | | |
L31M+Q54Y+Y93H | | | | | | |
L31V+P58A+Y93H | | | | | | |
L31V+P58S+Y93H | | | | | | |
L31V+Q54H+Y93H | | | | | | |
L31V+Q54H+Y93H | | 263x | resistance likely | | 8 | |
L31V+Q54Y+Y93H | | | | | | |
L31V+Q62E+Y93H | | | | | | |
Q54H+A92V+Y93H | | | | | | |
Q54H+P58A+Q62E | | | | | | |
Q54H+P58S+A92K | | | | | | |
Q54H+P58S+Y93H | | | | | | |
L28M+L31V+P58S+Y93N | | | | | | |
L28M+R30H+L31V+Y93H | | | | | | |
L28M+R30H+Q54H+Y93H | | | | | | |
L28M+R30Q+L31I+Y93H | | | | | | |
L28M+R30Q+L31V+Y93H | | | | | | |
L28M+R30Q+Q54H+A92T | | | | | | |
R30Q+L31M+P58S+Y93H | | | | | | |
R30Q+L31M+Q54H+Y93H | | | | | | |
R30Q+L31V+P58S+Y93H | | | | | | |
L31IM+Q54H+Q62E+Y93H | | | | | | |
L31I+Q54H+P58S+Y93H | | | | | | |
L31M+Q54H+A92E+Y93H | | | | | | |
L31M+Q54H+A92V+Y93H | | | | | | |
L31M+Q54H+P58S+Y93H | | | | | | |
L31M+Q54H+Q62E+Y93H | | | | | | |
L31M+Q54Y+P58S+Y93H | | | | | | |
L31V+Q54H+P58S+Y93H | | | | | | |
L31V+Q54H+Q62D+Y93H | | | | | | |
L31V+Q54H+Q62E+Y93H | | | | | | |
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1. Epclusa US Product Label. July 2016 |
2. Lawitz (2016) AAC 60(9):5368-5378. doi:10.1128/AAC.00763-16. |
3. Epclusa Canadian Product Label July 8, 2016 |
4. Sarrazin C, et al. 2017. Gastroenterology 152: S1062 |
5. Vosevi US Product Label 2017 |
6. Verrmhren et al. Www.natap.org/2017/AASLD_156.htm |
7. FDA Microbiology/Virology Reviews VoseviMicrobiology Reviews_2091950Orig1a000MicroR |
8.FDA Microbiology/Virology Reviews Epclusa_ 208341Orig1s000 (2015) |