Notes on HCV RAS
In the paper by Howe et al. they base their definitions of resistance mutations according to the “RAS variants listed in the 2020 EASL recommendations” (quote from the paper). I guess they mean the mutations listed in Table 7 in Pawlotsky et al. 2020:
| Drug class (genome region) | Amino acid position | Genotype/subtype | ||||||
|---|---|---|---|---|---|---|---|---|
| 1a | 1b | 2 | 3 | 4 | 5 | 6 | ||
| Nucleotide analogue (NS5B), e.g. sofosbuvir | ||||||||
| 150 | A150V | |||||||
| 159 | L159F | L159F | L159F | L159F | ||||
| 206 | K206E | |||||||
| 282 | S282G/R/T | S282G/R/T | S282G/R/T | S282G/R/T | S282C/G/R/T | S282G/R/T | S282G/R/T | |
| 316 | C316H/R | C316F/H/N | ||||||
| 320 | L320I/F/V | |||||||
| 321 | V321A | V321I | V321A | V321A | ||||
| NS5A inhibitors (NS5A) | ||||||||
| 24 | K24E/QR/T | Q24K | T24A/S | S24F | Q24H | |||
| 26 | K26E | |||||||
| 28 | M28A/G/S/T/V | L28A/M/T | L/F28C/S | M28T/K | L28M/S/T/V | L28I | F/L28A/I/L/M/T/V | |
| 29 | P29R | P29S, del29 | P29S | |||||
| 30 | Q30C/D/E/G/H/K/L/N/R/T/Y,del3 | R30G/H/P/Q/S | L30H/S | A30D/E/K/S | L30F/G/H/R/ S | Q30H | R30E/H/N/S | |
| 31 | L31I/F/M/P/V | L31F/I/M/V/W | L31I/M/V | L31F/I/M/P/V | M/L31I/V | L31F/I/V | L31I/M/V | |
| 32 | P32L/S,del32 | P32F/L/S,del32 | P32L | P32A/L/Q/R/S | ||||
| 38 | S38F | |||||||
| 58 | H58C/D/L/P/R | P58A/D/L/S/R/T | T58A/P/S | T58A/G/H/N/S | ||||
| 62 | Q/E62D | S62L | ||||||
| 92 | A92K/T | A92E/K/T/V | C92R/S/T/W | E92K | E92T | |||
| 93 | Y93C/F/H/L/N/R/S/T/W | Y93C/H/N/R/S/T | Y93F/N/H | Y93H/N/S | Y93C/H/N/ S/R/W | T93A/H/N/ S | ||
| Protease inhibitors (NS3) | ||||||||
| 36 | V36A/C/F/G/L/M | V36A/C/G/L/M | V36I | |||||
| 41 | Q41R | Q41R | Q41K | Q41R | Q41K/R | |||
| 43 | F43I/L/S/V | F43I/S/V | F43V | |||||
| 54 | T54A/S | T54A/C/G/S | ||||||
| 55 | V55I | V55A | V55A/I | |||||
| 56 | Y56H | Y56H/L/F | Y56H/F | Y56H | Y56H | Y56H | ||
| 80 | Q80K/L/R | Q80H/K/L/R | Q80K/R | Q80R | L80K/Q | |||
| 122 | S122G/N/R | S122A/D/G/I/N/R/T | S122T | |||||
| 155 | R155G/I/K/M/Q/S/T/V/W | R155C/G/I/K/L/Q/M/S/T/W | R155K | R155C/K | R155K | |||
| 156 | A156G/P/S/T/V | A156G/P/S/T/V | A156L/M/T/V | A156G/P/T/V | A156G/H/K/L/S/T/V | A156T/V | A156T/V | |
| 158 | V158I | V158I | ||||||
| 166 | A166S/T/Y | |||||||
| 168 | D168A/C/E/F/G/H/I/K/L/N/Q/R/T/V/Y | D168A/C/E/F/G/H/I/K/L/N/Q/T/V/Y | D168A/E/F/G/H/N/S/T/V/Y | Q168H/K/L/R | D168A/E/G/H/T/V | D168A/E/H/K/R/V/Y | D168A/E/G/H/V/Y | |
| 170 | I/V170T/V | I/V170A/L/T | I170V | |||||
| 175 | M175L | |||||||
| Non-nucleoside palm-1 inhibitor (NS5B), e.g. dasabuvir | ||||||||
| 314 | L314H | |||||||
| 316 | C316Y | C316H/N/Y/W | ||||||
| 368 | S368T | |||||||
| 395 | A395G | |||||||
| 411 | N411S | |||||||
| 414 | M414I/T/V | M414I/T/V | ||||||
| 445 | C445F/Y | |||||||
| 446 | E446K/Q | |||||||
| 448 | Y448C/H | Y448C/H | ||||||
| 553 | A553T/V | A553V | ||||||
| 554 | G554S | |||||||
| 555 | Y555H | |||||||
| 556 | S556G/R | S556G/R | ||||||
| 557 | G557R | |||||||
| 558 | G558R | G558R | ||||||
| 559 | D559G/N | D559G/N | ||||||
| 561 | Y561H/N | |||||||
| 565 | S565F |
Howe et al also has the follwing definitions of the various drugs against HCV:
| Target | Drugs |
|---|---|
| NS3 Protease Inhibitorer (PIs) | Simeprevir*, grazoprevir*, asunaprevir*, paritaprevir/r*, glecaprevir, voxilaprevir. |
| NS5A Replication Complex Inhibitors (NS5AIs) | Daclatasvir (DCV)*, ledipasvir (LDV)*, elbasvir*, ombitasvir*, pibrentasvir (PIB)*, velpatasvir (VEL)*. |
| NS5B polymerase nucleoside (NI) and non-nucleoside (NNI) inhibitors | NNI: dasabuvir (DSV)*. NI: sofosbuvir (SOF)*. |
* First generation
** Second generation
How does these correspond to the RAS identified by HCV GLUE? GLUE lists more than 500 different RAS, although a lot of these are different combinations of the same mutations. GLUE also divides the RAS into three categories, with Category I having the strongest evidence for association with resistance.
Leave a Comment