Hepatitis C virus resistance to new specifically-targeted antiviral therapy: A public health perspective

Table 1 Most important variations related to hepatitis C virus viral resistance to NS3 protease and NS5b polymerase in vitro and/or in vivo

Inhibitor class	Amino acid variations implicated in resistance
First generation NS3/A PI
Ciluprevir	(NS3) R155K/T/Q, A156V/T, D168A/V/T/H
Telaprevir	(NS3) V36M/A, T54A, R155K/T, A156V/T/S, V36M/A+R155K/T, V36M/A+A156V/T
Boceprevir	(NS3) V36M/A/L, T54S/A, R155K, V55A, R155T, A156S, V158I, V170A, I170T
Second generation NS3/A PI
Danoprevir	(NS3) R155K, D168E
Simeprevir	(NS3) Q80R/Q, R155K/T/Q, A156S/V/T, D168A/V/T/H
Asunaprevir	(NS3) R155K, A156V/T, D168A/E/T/V/Y
Narlaprevir	(NS3) V36A/M, R155K/T/Q, A156S/V/T, V170A
MK5172	(NS3) A156V/T, D168A/V/T/H
NS5A inhibitors
Daclatasvir	(NS5A) Q30R, L31 M/V, Y93C/N
NA polymerase inhibitors
Mericitabine	(NS5B) S282T in vitro, not reported in vivo
PSI-7977	Not reported in vivo
IDX-184	Not reported in vivo
INX-189	Not reported
NNI polymerase inhibitors
Tegobuvir	(NS5B) C316N, Y448H
Filibuvir	(NS5B) M423T/I/V, M426T, I482T
Setrobuvir	(NS5B) M414T/L, G554D, D559G
VCH-759	(NS5B) L419M/V, M423T/I/V, I482L/V/T, V494I/A
VCH-222	(NS5B) L419M, M423T, I482L
ABT-072	(NS5B) C316Y, M414T, Y448H/C, S556G

Summary from[11,17,18,77-80]. PI: Protease inhibitors; NA: Nucleos(t)ide analogs; NNI: Non-nucleos(t)idic (allosteric) inhibitors.