Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database

Table 1 Main amino acid substitutions found in the hepatitis C virus NS3 protease

	Amino acid (frequency %)
	HCV genotype
	1a			1b			2a		2b		3a
Position	wt	Variants		wt	Variants		wt	Variants	wt	Variants	wt	Variants
36	V (98.08)	L (1.6)	M (0.32)	L (0.74)	I (0.25)	V (99.01)	L (100)	-	L (100)	-	L (100)	-
80	Q (54.37)	K (44.66)	R (0.97)	Q (93.37)	K (0.25)	L (6.39)	G (100)	-	G (100)	-	Q (100)	-
155	R (99.36)	K (0.64)	-	R (99.50)	P (0.50)	-	R (100)	-	R (100)	-	R (100)	-
156	A (100)	-	-	A (100)	-	-	A (100)	-	A (100)	-	A (100)	-
168	D (99.36)	E (0.32)	G (0.32)	D (98.77)	A (0.25)	E (0.98)	D (100)	-	D (100)	-	Q (100)	-

Amino acids in bold are associated with resistance. wt: Wild-type; HCV: Hepatitis C virus.

Table 2 Main amino acid substitutions found in the hepatitis C virus NS5A protease

	Amino acid (frequency %)
	HCV genotype
	1a								1b								2a				2b				3a
Position	wt								wt								wt				wt				wt
28	M	94.38	I	0.37	T	0.75	V	4.49	L	97.17	M	2.27	V	0.52			F	100			L	100			M	96.46	I	3.57
30	Q	98.16	H	1.47	R	0.37			R	92.35	K	1.13	L/M	0.28	Q	5.95	K	94.74	R	5.26	K	100			A	96.46	L	3.57
31	L	98.88	M	1.12					L	96.03	M	3.40	I	0.57			M	84.21	L	15.79	M	76.92	L	23.08	L	100
93	Y	98.90	C	0.37	H	0.74			Y	95.75	H	4.25					Y	100			Y	100			Y	100

Amino acids in bold are associated with resistance. wt: Wild-type; HCV: Hepatitis C virus.

Table 3 Main amino acid substitutions found in the hepatitis C virus NS5A protease

	Amino acid (frequency %)
	HCV genotype
	1a				1b								2a	2b	3a
Position	wt				wt								wt	wt	wt
282	S	99.40	R	0.60	S								S	S	S
316	C				N	37.02	C	62.34	R/Y	0.32			C	C	C
556	S				N	89.24	D	0.98	G	7.82	N	1.95	G	G	G

Amino acid in bold are associated with resitance. wt: Wild-type; HCV: Hepatitis C virus.

Table 4 Resistance associated variants conferring resistance to direct antiviral agents¹

	euHCVdb		Los Alamos
	1a	1b	1a	1b
DAA	RAV	RAV	RAV	RAV
NS3
Simeprevir	V36M (0.32%)		V36M (0.44%)
	Q80K (44.66%)	Q80L (6.39%)	Q80K (36.62%)	Q80L (6.02%)
	S122G (4.49%)	S122G (9.07%)	n.a	n.a
	R155K (0.64%)		R155K (0.88%)
	D168E (0.32%)	D168E (0.98%)	D168E (0.29%)	D168E (0.80%)
				D170T (0.20%)
Paritaprevir	R155K (0.64%)		R155K (0.88%)
	D168E (0.32%)	D168E (0.98%)	D168E (0.29%)	D168E (0.80%)
Grazoprevir	A156T (0.00%)	A156T (0.00%)	A156T (0.00%)	A156T (0.00%)
	D168E (0.32%)	D168E (0.98%)	D168E (0.29%)	D168E (0.80%)
NS5A
Ledipasvir	M28T (0.75%)		n.a	n.a
	Q30H (1.47%)
	Q30R (0.37%)
	L31M (1.12%)
	Y93H (0.74%)	Y93H (4.25%)
	Y93C (0.37%)
Daclatasvir	M28T (0.75%)		n.a	n.a
	Q30H (1.47%)
	Q30R (0.37%)
	Y93H (0.74%)	Y93H (4.25%)
Ombitasvir	M28V (4.49%)	Y93H (4.25%)	n.a	n.a
Elbasvir	Q30H (1.47%)
	L31M (1.12%)
	Y93H (0.74%)	Y93H (4.25%)
NS5B
Sofosbuvir	S282T (0.00%)	S282T (0.00%)	S282T (0.00%)	S282T (0.00%)
Dasabuvir		C316N (37.02%)		C316N (36.17%)
		C316Y (0.32%)		C316Y (0.30%)
		N556G (7.82%)	N556G (0.42%)	N556G (8.21%)

¹DAAs recommended by the EASL and AASLD guidelines 2015. RAV: Resistance associated variants; DAAs: Direct antiviral agents; AASLD: American Association for the Study of Liver Diseases.