Table 2.
Dominant Mutations Associated With Resistance to NS3 Protease and NS5B Polymerase Inhibitors in Complete Genome Sequences of Hepatitis C Virus Genotypes 1–7
| Protein | Amino Acid Position | Dominant Amino Acid | Mutant Amino Acid | Drug | Substitution (% of Genomes), by Genotype |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Genotype 1 (n = 9) | Genotype 2 (n = 43) | Genotype 3 (n = 14) | Genotype 4 (n = 62) | Genotype 5 (n = 2) | Genotype 6 (n = 61) | Genotype 7 (n = 1) | |||||
| NS3 | 16 | C | S | ACH806 | ▪ | A (77)/S (2)/T (21) | T (100) | A (100) | T (100) | T (100) | |
| NS3 | 36 | V | AMLG | Telaprevir, boceprevir, SCH900518 | ▪ | L (100) | L (100) | L (100) | L (100) | V (75)/L (20)/ I (5) | L (100) |
| NS3 | 39 | A | V | ACH806 | ▪ | V (98)/I (2) | A (65)/S (14)/T (21) | A (92)/T (8) | ▪ | A (97)/T (1.5)/ D (1.5) | S (100) |
| NS3 | 41 | Q | R | Boceprevir, ITMN-191 | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ |
| NS3 | 43 | F | SC | ITMN-191, telaprevir, boceprevir | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ |
| NS3 | 54 | T | AS | Telaprevir, boceprevir, SCH900518 | T (89)/S (11) | ▪ | ▪ | T (97)/S (3) | ▪ | ▪ | G (100) |
| NS3 | 109 | R | K | SCH6 | ▪ | ▪ | ▪ | R (100) | ▪ | ▪ | ▪ |
| NS3 | 138 | S | T | ITMN-191 | ▪ | ▪ | ▪ | S (98)/F (2) | ▪ | S (98.5)/F (1.5) | ▪ |
| NS3 | 155 | R | K,T,I,M, G,L,S,Q | Telaprevir, boceprevir, TMC 435, R7227, MK 7009, BI 201335, SCH900518, BILN-2061 | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ |
| NS3 | 156 | A | STVI | Telaprevir, boceprevir, R7227, SCH900518, BILN-2061 | ▪ | ▪ | ▪ | ▪ | ▪ | A (98.5)/V (1.5) | ▪ |
| NS3 | 168 | D | QAVET | TMC 435, R7227, MK 7009, BI201335, BILN-2061 | ▪ | ▪ | Q (100) | ▪ | D (50)/E (50) | D (97)/E (3) | Q (100) |
| NS3 | 170 | V | AT | Telaprevir, boceprevir | V (56)/I (44) | I (95)/V (2.5) /unresolved (2.5) | I (71)/V (29) | V (97)/I (3) | I (50)/V (50) | V (65.5)/A (1.5)/I (33) | ▪ |
| NS3 | 489 | S | L | ITMN-191 | S (67)/V (33) | V (100) | V (100) | S (89)/A (9)/V (2) | V (100) | V (85)/I (15) | ▪ |
| NS5B | 95 | H | Q | A-782759 | ▪ | ▪ | ▪ | ▪ | ▪ | H (97)/C (1.5)/R (1.5) | ▪ |
| NS5B | 96 | S | T | R1479 | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ |
| NS5B | 282 | S | T | 2'C-methyl- ribonucleosides | ▪ | ▪ | ▪ | S (98)/T (2) | ▪ | ▪ | ▪ |
| NS5B | 316 | C | Y | HCV-796, A-837093 | C (89)/N (11) | C (98)/W (2) | ▪ | C (87)/N (8)/H (5) | ▪ | ▪ | ▪ |
| NS5B | 365 | S | TA | HCV-796 | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ |
| NS5B | 411 | N | S | A-782759 | ▪ | ▪ | N (93)/S (7) | ▪ | ▪ | ▪ | ▪ |
| NS5B | 414 | M | LT | A-782759 | ▪ | Q (98)a | ▪ | L (53)/V (32)/I (13)/Q (2) | ▪ | M (98.5)/A (1.5) | ▪ |
| NS5B | 423 | M | TVI | AG-021541 | ▪ | ▪a | ▪ | ▪ | I (100) | ▪ | ▪ |
| NS5B | 448 | Y | HC | A-782759, A-837093 | ▪ | ▪a | ▪ | ▪ | ▪ | ▪ | ▪ |
| NS5B | 495 | P | LA | JTK-109 | ▪ | ▪a,b | ▪c | ▪e | ▪ | P (98.5)/L (1.5) | ▪ |
| NS5B | 554 | G | DS | A-837093 | ▪ | G (74)/S (21)a,b | ▪c,d | ▪e,f | ▪ | ▪ | C (100) |
| NS5B | 559 | D | GSN | A-837093 | ▪ | D (93)/H (2)a,b | ▪c,d | ▪e,f | ▪ | ▪ | ▪ |
Filled squares indicate that the dominant residue found in genotype 1 is found in 100% of the genomes analyzed for any given genotype. Substitutions known to confer drug resistance are in bold, and substitutions of unknown impact are in italics.
Abbreviation: AA, amino acid.
a No data at this position for G1727_2m_QC76.
b No data at this position for DQ430815_2b_TN9-0FL.
c No data at this position for AY956467_3a_32E and DQ430819_3a_TN78-0.
d No data at this position for G1245_3i_PB98686.
e No data at this position for DQ988079_4a_Eg12 and DQ988073_4a_Eg2.
f No data at this position for EF589160_4f_IFBT84, DQ988074_4a_Eg3, DQ988075_4a_Eg4, DQ988076_4a_Eg7, DQ988077_4a_Eg9, DQ988078_4a_Eg10, and G1726_4n_PB58378.