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Table 4 Amino acid mutations in the HCV NS5B protein in DAA-naïve patients infected with HCV genotypes 1a (n = 32) or 1b (n = 30)

From: Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-naïve patients

 

NS5B mutations in DAA-naïve patients

DAAs

Genotype 1a

Fold change in EC50

Genotype 1b

Fold change in EC50

References

 

S96Tγ

 

S96T

  
 

N142T

 

N142T

  

Sofosbuvir + Mericitabine

L159F

 

L159F (7/30, 23.3%)

Xβ

[32]

 

C223H/Y

 

C223H/Y

  
 

S282T

 

S282T

  
 

L320F

 

L320F

  

PSI-352938

V321I (1/32, 3.1%) α

2.0

V321I (1/30, 3.3%)

2.0

[17, 33]

Tegobuvir + HCV796

C316Y/N/F/S

 

C316N (11/30, 36.6%)

3.0-5.2

[17, 34]

 

V362A

 

V362A

  
 

S365A/T

 

S365A/T

  
 

M414T

 

M414T

  
 

L419M/S

 

L419M/S

  
 

A421V

 

A421V

  
 

R422K

 

R422K

  
 

M423I/V/T

 

M423I/V/T

  

Filibuvir

M426L (1/32, 3.1%)

0.8

M426L (2/30, 6.6%)

0.8

[21]

 

C445F

 

C445F

  

Tegobuvir

Y448H (1/32, 3.1%)

36.0

Y448H

 

[34]

Tegobuvir

Y452H (1/32, 3.1%)

6.9

Y452H (1/30, 3.3%)

6.9

[34]

Tegobuvir

R465G

 

R465G (1/30, 3.3%)

1.1

[34]

 

I482L/T

 

I482L/T

  
 

A486V

 

A486V

  
 

V494A

 

V494A

  
 

P495A/L/S/T

 

P495A/L/S/T

  
 

P496A/S

 

P496A/S

  

JTK-109 + Deleobuvir

A499T

 

V499A (4/30, 13.3%)

3.0

[17, 35]

 

G554D

 

G554D

  
 

S556G/D/N

 

S556G/D/N

  
 

D559G/N

 

D559G/N

  
  1. αAmino acid changes conferring resistance to NS5B inhibitors are reported in italics. The number and % of patients with mutated strains is reported in brackets. βResistance levels are reported only when associated with L320F. GeneBank NS5B reference sequence accession number for HCV genotype 1a is AF009606, and for genotype 1b, AY045702.