NVR 3-778 is a first-in-class, orally bioavailable HBV CAM belonging to the SBA class, exhibiting anti-HBV activity.

NVR 3-778 inhibits the generation of infectious HBV DNA-containing virus particles with a mean antiviral (EC50: 0.40?μM in HepG2.2.15 cells). NVR 3-778 inhibits pregenomic RNA encapsidation, viral replication, and the production of HBV DNA- and HBV RNA-containing particles. NVR 3-778 also inhibits de novo infection and viral replication in primary human hepatocytes with EC50s of 0.81?μM against HBV DNA and between 3.7μM and 4.8?μM against the production of HBV antigens and intracellular HBV RNA. NVR 3-778 targets HBV core protein and inhibits viral replication. NVR 3-778 has pan-genotypic antiviral activity and a lack of cross-resistance with nucleos(t)ide inhibitors of HBV replication. The EC50 values of NVR 3-778 are increased by 4.5-, 9.3-, and 15.8-fold in the presence of 10%, 20%, and 40% human serum, respectively.

In dogs following oral administration, NVR 3-778 (1.5?mg/kg; i.g.) shows the mean Cmax and AUC0–inf values of 0.56?μg/ml and 3.50?μg·h/ml, respectively. And the mean oral bioavailability is determined to be 84.6%.