Research progress of the related resistance mutations of direct-acting antiviral agents for HCV infection treatment

doi:10.3877/cma.j.issn.1674-1358.2016.05.005

Abstract

Abstract:

In recent years, the development of direct-acting antiviral agents (DAAs) has made a breakthrough and had a variety of advantages of a high SVR rate, a wide genotype spectrum, a short treatment cycle and a low resistance rate in the treatment for HCV infection process. With the development of new antiviral drugs in clinical application, it has been found that the efficacy of treatment for HCV infection was directly affected by some related resistance loci. In this paper, the new DAAs drugs (including NS3/4A protease inhibitors, NS5A inhibitors and NS5B polymerase inhibition) and the related drug resistance loci were summarized.

Key words: Hepatitis C virus, Genotype, Direct-acting antiviral agents inhibitor, Resistance mutations

Danhui Sun, Xuebing Yan. Research progress of the related resistance mutations of direct-acting antiviral agents for HCV infection treatment[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2016, 10(05): 534-540.

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References 38

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耐药位点	HCV NS3/4A蛋白酶抑制剂
耐药位点	Boceprevir	Telaprevir	Simprevir	Faldaprevir	ABT-450	Danoprevir
36	V36A/M	V36A/M/G/L	V36M		V36M/A/G	V36M/A/G
43			F43S
54	T54A/S/G/C	T54A/S	T54S
55	V55A/I				V55I	V55I
80			Q80K/R/L
122			S122A/R
132		I132V**
138			S138T
155	R155K/T	R155K/T/G/M	R155K	R155K	R155K	R155K
156	A156S/T/V	A156S/T/V	A156T/V	A156T/V	A156T/V
158	V158I
168		D168N^**	D168A/V/E/H/T	D168A/V/E/H/Y/N/P/I	D168A/V/Y/E/K	D168E/T
170	I^V170F^A/T^*T
175	M175L

耐药位点	HCV NS3/4A蛋白酶抑制剂
耐药位点	Boceprevir	Telaprevir	Simprevir	Faldaprevir	ABT-450	Danoprevir
36	V36A/M	V36A/M/G/L	V36M		V36M/A/G	V36M/A/G
43			F43S
54	T54A/S/G/C	T54A/S	T54S
55	V55A/I				V55I	V55I
80			Q80K/R/L
122			S122A/R
132		I132V**
138			S138T
155	R155K/T	R155K/T/G/M	R155K	R155K	R155K	R155K
156	A156S/T/V	A156S/T/V	A156T/V	A156T/V	A156T/V
158	V158I
168		D168N^**	D168A/V/E/H/T	D168A/V/E/H/Y/N/P/I	D168A/V/Y/E/K	D168E/T
170	I^V170F^A/T^*T
175	M175L

DAAS	GT1a	EC₅₀增加倍数	GT1b	EC₅₀增加倍数
Daclatasvir	M28V（3.1%）	1.3	L28M/V	2.0
	Q30E/H/R/K		R30H
	L31M（3.1%）	341	L31M（6.6%）	3
Ledipasvir	L31M（3.1%）	140	L31M
GSK805	L31M（3.1%）	> 150	L31M
	I280V		I280V（6.6%）
	V298A		V298A
	V362A		V362A
	S364P		S364P
	S368P		S368P
Samatasvir	L31M		L31M（6.6%）
	p32L		P32L
	Y93C/H/N		Y93H（10%）	3.6
	V153M		V153M
	R157W		R157W
	V198V		V198A	93
	M202L		M202L
	P223S		P223S
	M265V		M265V

Daclatasvir	Q54H/L/N		Q54H（26.6%）	1.0
Daclatasvir	H58P（6.2%）	1.2			P58S/T/L
	N69T	N69T
	A92V	A92V
Daclatasvir	Y93C/H/N		Y93H（10%）	24
Ledipasvir	Y 93C/H/N		Y93H（10%）	1 319

DAAS	GT1a	EC₅₀增加倍数	GT1b	EC₅₀增加倍数
Daclatasvir	M28V（3.1%）	1.3	L28M/V	2.0
	Q30E/H/R/K		R30H
	L31M（3.1%）	341	L31M（6.6%）	3
Ledipasvir	L31M（3.1%）	140	L31M
GSK805	L31M（3.1%）	> 150	L31M
	I280V		I280V（6.6%）
	V298A		V298A
	V362A		V362A
	S364P		S364P
	S368P		S368P
Samatasvir	L31M		L31M（6.6%）
	p32L		P32L
	Y93C/H/N		Y93H（10%）	3.6
	V153M		V153M
	R157W		R157W
	V198V		V198A	93
	M202L		M202L
	P223S		P223S
	M265V		M265V

Daclatasvir	Q54H/L/N		Q54H（26.6%）	1.0
Daclatasvir	H58P（6.2%）	1.2			P58S/T/L
	N69T	N69T
	A92V	A92V
Daclatasvir	Y93C/H/N		Y93H（10%）	24
Ledipasvir	Y 93C/H/N		Y93H（10%）	1 319

DAAS	GT1a	EC₅₀增加倍数	GT1b	EC₅₀增加倍数
Sofosbuvir + Mericitabine	S96T		S96T
	N142T		N142T
	L159F		L159F（23.3%）
	C223H/Y		C223H/Y
	S282T		S282T
	L320F		L320F
PSI-352938	V321I（3.1%）	2.0	V321I（3.3%）
Tegobuvir + HCV796	C316Y/N/F/S		C316N（36.6%）
	V362A		V362A
	S365A/T		S365A/T
	M414T		M414T
	L419M/S		L419M/S
	A421V		A421V
	R422K		R422K
	M423I/V/T		M423I/V/T
Filibuvir	M426L（3.1%）	0.8	M426L（6.6%）	0.8
Filibuvir	C445F		C445F
Tegobuvir	Y448H（3.1%）		Y448H
	Y452H（3.1%）		Y452H（3.3%）
	R465G		R465G（3.3%）
	I482L/T	36.0	I482L/T	6.9
	A486V	6.9	A486V	1.1
	V494A		V494A
	P495A/L/S/T		P495A/L/S/T
	P496A/S		P496A/S
JIK109 + Deleobuvir	A499T		V499A（13.3%）	3.0
	G554D		G554D
	S556G/D/N		S556G/D/N
	D559G/N		D559G/N

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