Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model

Table 1 Inhibition of hepatitis C virus infectivity and 50% effective concentration of hepatitis C virus replication with direct active antivirals and autophagy inhibitors

Drugs1	Infectivity inhibition (%)	Average (SD)2	Replication inhibition (EC50)3	Average (SD)4	CC50 (SD)5
INF (2.6 to 260 nmol/L)6	Up to 95%	5	17 ng/mL	7.2	40 ng/mL (± 4)
RBV (1 to 100 μmol/L)	3% to 37%	3	146 μmol/L	13	400 μmol/L (± 21)
7TVR (0.01 to 50 μmol/L)	62% to 89%	4	0.395 μmol/L	0.038	40 μmol/L (± 3)
7BOC (0.01 to 50 μmol/L)	61% to 95%	5	0.417 μmol/L	0.024	41 μmol/L (± 5)
7SOF (0.01 to 50 μmol/L)	75% to 95%	4	0.147 μmol/L	0.017	23 μmol/L (± 2)
7HCQ (0.1 to 50 μmol/L)	25% to 94%	4	1.17 μmol/L	0.023	27 μmol/L (± 2)
7GNS-396 (0.01 to 5 μmol/L)	6% to 93%	3	0.158 μmol/L	0.014	25 μmol/L (± 2)
INF (2.6 to 260 nmol/L)/RBV 100 μmol/L	Up to 98%	6	10 ng/mL	3.1	43 ng/mL (± 4)
7HCQ (0.1 to 5 μmol/L)/RBV 50 μmol/L	27% to 85%	2	0.456 μmol/L	0.044	31 μmol/L (± 3)
7GNS-396 (0.01 to 5 μmol/L)/RBV 100 μmol/L	9% to 94%	2	0.157 μmol/L	0.012	26 μmol/L (± 2)
7TVR (0.01 to 50 μmol/L)/RBV 100 μmol/L	Up to 98%	3	0.310 μmol/L	0.029	49 μmol/L (± 3)
7BOC (0.01 to 50 μmol/L)/RBV 100 μmol/L	Up to 95%	2	0.370 μmol/L	0.035	48 μmol/L (± 4)
7SOF (0.01 to 50 μmol/L)/RBV 100 μmol/L	Up to 100%	2	0.080 μmol/L	0.028	17 μmol/L (± 5)
7TVR 1 μmol/L/7BOC 1 μmol/L	Up to 89%	2	0.410 μmol/L	0.039	50 μmol/L (± 3)
7TVR 1 μmol/L/INF 26 nmol/L/RBV 100 μmol/L	Up to 99%	3	0.315 μmol/L	0.031	44 μmol/L (± 4)
7BOC 1 μmol/L/INF 26 nmol/L/RBV 100 μmol/L	Up to 97%	2	0.350 μmol/L	0.033	47 μmol/L (± 3)
7SOF 1 μmol/L/INF 26 nmol/L/RBV 100 μmol/L	Up to 100%	3	0.055 μmol/L	0.029	18 μmol/L (± 3)

¹Drugs added at day 4 post-infection for 6 d;

²Average (SD) of infectivity inhibition at day 6 post-treatment;

³EC50 of the drugs written in bold at day 6 post-treatment;

⁴Average (SD) of EC50 at day 6 post-treatment;

⁵CC50 (SD): 50% cytotoxic concentration of the drugs written in bold at day 6 post-treatment (standard deviation);

⁶INF 26 nmol/L: Peg-INF concentration corresponding to SOC;

⁷DAAs and autophagy inhibitors in bold. EC50: 50% effective concentration; BOC: An inhibitor of the HCV-encoded NS3 protein; TVR: An inhibitor of the HCV-encoded NS3/4A hepatitis C protease; SOF: An uridine analogue inhibitor of the HCV NS5B polymerase; HCV: Hepatitis C virus; TVR: Telaprevir; BOC: Boceprevir; SOF: Sofosbuvir; RBV: Ribavirin; SD: Standard deviation; Peg-INF: Pegylated-interferon α-2a; DAAs: Direct acting antivirals; HCQ: Hydroxychloroquine.