Table 2. Differential time requirements for RR induction in HEp-2 cells treated with different CTPS1 and IMPDH2 inhibitors at 2 mM concentration.

	Percent HEp-2 cells with RR (total counted); number of experiments
Time after addition	Ribavirin1	DON2	Acivicin3
0 min	0% (300); n = 3	0% (300); n = 3	0% (300); n = 3
30 min4	15.2% (67); n = 2	8.3% (120); n = 1	5.2% (102); n = 1
1 h5	98.1% (53); n = 2	13.7% (80); n = 3	11.5% (87); n = 3
2 h5	95.2% (42); n = 2	20.2% (89); n = 2	19.3% (119); n = 2
3 h6	98.1% (55); n = 2	70.5% (88); n = 3	39.4% (109); n = 2
24 h7	98.2% (231); n = 3	94.8% (98); n = 5	97.3% (226); n = 4

¹Ribavirin induced RR as early as 30 min and between 1 to 24 h, nearly all cells had RR (p<0.0001, 0 min vs all time points and 30 min vs 1 to 24 h). There is no statistical significance between 1 to 24 h after Bonferroni's adjustment;

²Induction of RR by DON was slower than Ribavirin (p<0.0001, 1, 2, and 3 h; ns, 30 min and 24 h) and the percentage of RR positive cells gradually increased after 1–3 h and was nearly all cells at 24 h.

³Acivicin had similar pattern to DON in which RR positive cells gradually increased after 1 h and nearly all cells at 24 h.

⁴Ribavirin vs DON and DON vs Acivicin, ns; Ribavirin vs Acivicin, p = 0.03;

⁵Ribavirin vs DON and Ribavirin vs Acivicin, p<0.0001; DON vs Acivicin, ns;

⁶Ribavirin vs DON, DON vs Acivicin, Ribavirin vs Acivicin, p<0.0001;

⁷ns between Ribavirin, DON, and Acivicin.