NS3 GT2

Download full data set for GT2

Asunaprevir

Mutation	EC50 (nM)	Fold-shift	Phenotype	Clinical RAS	Reference	Comments
WT (2a_JFH1)	230		resistance likely	No
WT (2b) [not used as reference in algorithm]	248		resistance likely	No
G15D
L36A
L36D
L36M
L36P
L36V
Q41V
Q41K
S42T
F43S
F43V
T54A
T54S
V55A
V55I
V55S
Y56F
Y56H
A78V
E79G
E79D
G80Q
G80E
G80H
G80I
G80K
G80L
G80M
G80R
G80T
V107I
K122I
K122R
K122S
K122T
I132L
I132V
P146S
A150V [Conflicting WT, not used in algorithm]
F154Y
R155G
R155K
R155T
R155W
A156G
A156L
A156M
A156S
A156T
A156V
V158I
S 160T
A166S (GT2b) [Conflicting WT, not used in algorithm]
D168A
D168E
D168F
D168G
D168H
D168I
D168K
D168L
D168N
D168T
D168V
D168Y
D 168S
I170A
I170T
I170G
I170V
E173G
V 178T
A178V [Conflicting WT]
G15D+A156T
G15D+A156V
V36M+R155K
V55A+D168E
V55I+D168E
Y56F+D168A
Y56F+D168V
Y56F+D168E
Y56F+R122G
Y56H+D168A
Y56H+D168E
Y56H+D168V
E79G+F154Y
F154Y+E173G
A160T+D168V
A160T+D168Y
D168V+A178T
D168V+A178V
L36M+F43L+G80W+R122L+R155M+D168Y+L175I

1.  Sunvepra Canadian Prodcut Monograph 2016

Glecaprevir

Mutation	EC50 (nM)	Fold-shift	Phenotype	Clinical RAS	Replicative Fitness (1)	Reference	Comments
WT (2a_JFH1)	2.2 (2.2-4.6)	1x	likely susceptible		100	1	clinical isolate=0.3 (0.05-3.8)
WT (2b) [not used as reference in algorithm]	3.1	1x	likely susceptible			1
G15D	1.1	0.5x	likely susceptible		85	1
L36A
L36D
L36M
L36P
L36V
Q41V
Q41K
S42T
F43S
F43V
T54A
T54S
V55A	2.3	0.9x	likely susceptible		51	1
V55I	3.1	1.2x	likely susceptible		43	1
V55S
Y56F	1.7	0.7x	likely susceptible		70	1	GT2b
Y56H	1.4	0.6x	likely susceptible		125	1	GT2b
A78V
E79G	5.8	1.9x	likely susceptible			1	GT2b
E79D
G80Q
G80E
G80H
G80I
G80K
G80L
G80M
G80R
G80T
V107I
K122I
K122R
K122S
K122T
I132L			Resistance possible	Yes		1	Clinical VF RAV (1)
I132V
P146S	4	1.3x	likely susceptible			1	GT2b
A150V [Conflicting WT, not used in algorithm]	2.4	0.8x	likely susceptible			1	GT2b
F154Y	2.8	0.9x	likely susceptible			1	GT2b
R155G
R155K
R155T
R155W
A156G
A156L
A156M	3370	1087x	resistance likely			1	Gt2b
A156S
A156T	541	216x	resistance likely		69	1	GT2b 148x
A156V	2857	1143x	resistance likely		43	1	GT2b 1455x
V158I
S 160T	3.2	1x	likely susceptible			1	GT2b
A166S (GT2b) [Conflicting WT, not used in algorithm]
D168A	4.8	1.9x	likely susceptible		75	1	GT2b 1.3x
D168E	8.1	3.3x	Resistance possible		116	1	GT2b 2.1x
D168F	12.3	4x	Resistance possible			1	GT2b
D168G
D168H	7.9	3.2x	Resistance possible		86	1	GT2b 2.7x
D168I
D168K
D168L
D168N
D168T	17.4	5.6x	Resistance possible			1	GT2b
D168V	4.9	2.0x	likely susceptible		129	1	GT2b 2.9x
D168Y	6	2.4x	likely susceptible		107	1	GT2b 2.1x
D 168S	3.8	1.2x	likely susceptible			1	GT2b
I170A
I170T
I170G
I170V
E173G	7.4	2.4x	likely susceptible			1
V 178T	1.9	0.6x	likely susceptible			1	GT2b
A178V [Conflicting WT]	3	1.0x	likely susceptible			1	GT2b
G15D+A156T	871	348x	resistance likely		64	1
G15D+A156V	3470	1388x	resistance likely		49	1
V36M+R155K
V55A+D168E	9.6	3.8x	Resistance possible		86	1
V55I+D168E	6.6	2.7x	Resistance possible		69	1
Y56F+D168A	2.3	0.8x	likely susceptible			1	GT2b
Y56F+D168V	8.1	2.6x	Resistance possible			1	GT2b
Y56F+D168E	4	1.6x	likely susceptible		160	1
Y56F+R122G
Y56H+D168A	2.3	0.9x	likely susceptible		85	1
Y56H+D168E	4.6	1.8x	likely susceptible		61	1
Y56H+D168V	7.5	3x	Resistance possible		100	1
E79G+F154Y	20.9	6.7x	Resistance possible			1	GT2b
F154Y+E173G	19.1	6.1x	Resistance possible			1	GT2b
A160T+D168V	17.1	5.5x	Resistance possible			1	GT2b
A160T+D168Y	12.3	4x	Resistance possible			1	GT2b
D168V+A178T	13	4.2	Resistance possible			1	GT2b
D168V+A178V	17.7	5.7	Resistance possible			1	GT2b
L36M+F43L+G80W+R122L+R155M+D168Y+L175I

1. FDA Microbiology/Virology Mayvret Review    https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209394Orig1s000MicroR.pdf

Grazoprevir

Mutation	EC50 (nM)	Fold-shift	Phenotype	Clinical RAS	Reference	Comments
WT (2a_JFH1)
WT (2b) [not used as reference in algorithm]
G15D
L36A
L36D
L36M
L36P
L36V
Q41V
Q41K
S42T
F43S
F43V
T54A
T54S
V55A
V55I
V55S
Y56F					1	Clinical RAV?
Y56H
A78V
E79G
E79D
G80Q
G80E
G80H
G80I
G80K
G80L
G80M
G80R
G80T
V107I
K122I
K122R					1	Clinical RAV?
K122S
K122T
I132L					1	Clinical RAV?
I132V
P146S
A150V [Conflicting WT, not used in algorithm]
F154Y
R155G
R155K
R155T
R155W
A156G
A156L
A156M
A156S
A156T
A156V
V158I
S 160T
A166S (GT2b) [Conflicting WT, not used in algorithm]
D168A
D168E
D168F
D168G
D168H
D168I
D168K
D168L
D168N
D168T
D168V
D168Y
D 168S
I170A
I170T
I170G
I170V
E173G
V 178T
A178V [Conflicting WT]
G15D+A156T
G15D+A156V
V36M+R155K
V55A+D168E
V55I+D168E
Y56F+D168A
Y56F+D168V
Y56F+D168E
Y56F+R122G
Y56H+D168A
Y56H+D168E
Y56H+D168V
E79G+F154Y
F154Y+E173G
A160T+D168V
A160T+D168Y
D168V+A178T
D168V+A178V
L36M+F43L+G80W+R122L+R155M+D168Y+L175I

1. Serfaty et al. EASL 2017 http://www.natap.org/2017/EASL/EASL_06.htm

Paritaprevir

Mutation	EC50 (nM)	Fold-shift	Phenotype	Clinical RAS	Reference	Comments
WT (2a_JFH1)	5.3					L36, G80, R122, S166=RAS
WT (2b) [not used as reference in algorithm]
G15D
L36A
L36D
L36M
L36P
L36V
Q41V
Q41K
S42T
F43S
F43V
T54A
T54S
V55A
V55I
V55S
Y56F
Y56H
A78V
E79G
E79D
G80Q
G80E
G80H
G80I
G80K
G80L
G80M
G80R
G80T
V107I
K122I
K122R
K122S
K122T
I132L
I132V
P146S
A150V [Conflicting WT, not used in algorithm]
F154Y
R155G
R155K
R155T
R155W
A156G
A156L
A156M
A156S
A156T
A156V
V158I
S 160T
A166S (GT2b) [Conflicting WT, not used in algorithm]
D168A
D168E
D168F
D168G
D168H
D168I
D168K
D168L
D168N
D168T
D168V
D168Y
D 168S
I170A
I170T
I170G
I170V
E173G
V 178T
A178V [Conflicting WT]
G15D+A156T
G15D+A156V
V36M+R155K
V55A+D168E
V55I+D168E
Y56F+D168A
Y56F+D168V
Y56F+D168E
Y56F+R122G
Y56H+D168A
Y56H+D168E
Y56H+D168V
E79G+F154Y
F154Y+E173G
A160T+D168V
A160T+D168Y
D168V+A178T
D168V+A178V
L36M+F43L+G80W+R122L+R155M+D168Y+L175I

\

1. Viekira Pak US Product Label jan 28, 2016

Voxilaprevir

Mutation	EC50 (nM)	Fold-shift	Phenotype	Clinical RAS	Reference	Replication Capacity (%WT)	Comments
WT (2a_JFH1)	3.04 (SD 1.89)	1x	likely susceptible		3,1	100 (4)	mean of 64 clinical isolates
WT (2b) [not used as reference in algorithm]
G15D
L36A
L36D		unfit					GT2a
L36M			likely susceptible		3		GT2a
L36P		unfit					GT2a
L36V		<1.2	likely susceptible		4
Q41V			likely susceptible		3		GT2a
Q41K					4		clinical TE RAV , 1% (4)
S42T		<1.2	likely susceptible		4
F43S
F43V		2.5x - 20x	Resistance possible		3,1		GT2b
T54A
T54S
V55A
V55I			likely susceptible		3		GT2b
V55S			likely susceptible		3		GT2a
Y56F			likely susceptible		3,4		Gt2a/2b
Y56H
A78V		<1.2x	likely susceptible		4
E79G
E79D		<1.2x	likely susceptible		4
G80Q		<1.2x	likely susceptible		4
G80E			likely susceptible		3		GT2b
G80H
G80I
G80K
G80L
G80M
G80R
G80T			likely susceptible		3		GT2b
V107I
K122I			likely susceptible		3		GT2a
K122R			likely susceptible		3		GT2a
K122S		<1.2x	likely susceptible		4
K122T			likely susceptible		3		GT2a
I132L		<1.2x	likely susceptible		4
I132V		<1.2x	likely susceptible		4
P146S
A150V [Conflicting WT, not used in algorithm]
F154Y
R155G		unfit			3		GT2a/2b
R155K
R155T
R155W		unfit			3		GT2a/2b
A156G			likely susceptible		3		GT2b
A156L		246x	resistance likely		4,2,3	34.7 (4)	GT2a
A156M
A156S					1
A156T		38x	resistance likely		4,3	21 (4)	GT2a (2b unfit)
A156V		>129x	resistance likely		4,2,3	7.7 (4)	GT2a (2b unfit)
V158I
S 160T
A166S (GT2b) [Conflicting WT, not used in algorithm]			likely susceptible		3		GT2a/2b
D168A
D168E		1.6x	likely susceptible		3	85.7 (4)	GT2a
D168F
D168G
D168H
D168I
D168K			likely susceptible		3		GT2a (2b unfit)
D168L
D168N
D168T
D168V			likely susceptible		3		GT2a (2b unfit)
D168Y			likely susceptible		3		GT2b
D 168S			likely susceptible		3		GT2a
I170A
I170T
I170G		unift			3		GT2a
I170V		<1.2	likely susceptible		4
E173G
V 178T
A178V [Conflicting WT]
G15D+A156T
G15D+A156V
V36M+R155K
V55A+D168E
V55I+D168E
Y56F+D168A
Y56F+D168V
Y56F+D168E
Y56F+R122G		0.9x	likely susceptible		3
Y56H+D168A
Y56H+D168E
Y56H+D168V
E79G+F154Y
F154Y+E173G
A160T+D168V
A160T+D168Y
D168V+A178T
D168V+A178V
L36M+F43L+G80W+R122L+R155M+D168Y+L175I		0.8x	likely susceptible		3

1. Sarrazin C, et al. 2017. Gastroenterology 152: S1062

2. Vosevi US Product label 2017

3. Dvory-Sobol H et al 2017 AASLD.  http://www.natap.org/2017/AASLD/AASLD_29.htm

4. FDA Vosevi Microbiology Reviews 209195Orig1s000MicroR