TABLE 3.

Amino acid substitutions and phenotypic changes observed in the resistance selection with PSI-6130 and R7128 in replicon cells

Selection set	Passage no.	PSI-6130/R7128 concn (μM)	EC50 fold shifta	Amino acid substitution(s) in NS5B
Untreated	35	0	No shift	No substitutions
Untreated	56	0	No shift	No substitutions
1	6	5	7	Y586C
1	28	50	32	S282S/T, C575S, Y586C
1	53	100	51	S282T, K81R, S84S/P I239L, A300A/T, L320F/L/C, A421V, Y586C
2	25	50	NDb	S282S/T, I239V, A396G
2	27	25	25	S282T, A396G
2	28	25	ND	S282T, I239L, A396G, V485L
2	32	25	13	S282T, I239L, A396G
3	21	30	120	K72M, S282S/T
3	26	30	107	K72M, S282T, L564M

^aShift calculated as EC₅₀ for selected cells divided by the EC₅₀ for untreated cells.

^bND, not determined.