TABLE 2.
Antiviral properties measured as EC50 values for different markers in HBV-infected PHHs
| Day, compound | Median EC50 (range) (nM) for indicated marker; no of exptsa
|
|||
|---|---|---|---|---|
| Extracellular HBV DNA | Total intracellular HBV RNA | HBe/cAg | HBsAg | |
| Zero | ||||
| JNJ-6379 | 93 (46 to 188); 8 | 876 (535 to 1,339); 6 | 960 (794 to 1,326); 8 | 1,608 (916 to 3,827); 6 |
| TDF | <8.0 (ND); 1 | >5,000 (ND); 1 | >5,000 (ND); 1 | >5,000 (ND); 1 |
| ETV | 0.023 (0.014 to 0.023); 3 | >5,000 (>1.0 to >5,000); 17 | >5,000 (>1.0 to >5,000); 19 | >5,000 (>1.0 to >5,000); 22 |
| 4 or 5 | ||||
| JNJ-6379 | 102 (52 to 137); 8 | >25,000 (>5,000 to >25,000); 8 | >25,000 (>5,000 to >25,000); 8 | >25,000 (>5,000 to >25,000); 8 |
| TDF | <8.0 (ND); 1 | >5,000 (ND); 1 | >5,000 (ND); 1 | >5,000 (ND); 1 |
| ETV | 0.028 (0.012 to 0.028); 3 | >5,000 (>1.0 to >5,000); 23 | >5,000 (>1.0 to >5,000); 23 | >5,000 (>1.0 to >5,000); 23 |
a
Stably HBV-replicating HepG2.2.15 cells were the source of HBV for the infection of cryopreserved PHHs. The antiviral properties of each compound were tested in a dose-response assay in HBV-infected PHHs. HBV DNA (extracellular) and HBV RNA (intracellular) levels were assessed using quantitative PCR (qPCR). HBe/cAg and HBsAg in the supernatants were evaluated by AlphaLISA. HBV, hepatitis B virus; PHHs, primary human hepatocytes; EC50, 50% effective concentration; HBe/cAg, hepatitis B e antigen and hepatitis B core-related antigen; HBsAg, hepatitis B surface antigen; ETV, entecavir; TDF, tenofovir disoproxil; ND, not determined.