Morphothiadin (GLS4) is a potent inhibitor on the replication of both wild-type and adefovir-resistant HBV (IC50 of 12 nM).

HBV:12 nM

Morphothiadin is a potent inhibitor of both wild-type and adefovir-resistant HBV (IC50 of 12 nM) and shows no toxicity up to 25 μM. The CC50 for primary hepatocytes is 115 μM (P<0.001), while the CC90 in HepAD38 cells is 190 μM (P<0.01). Morphothiadin strongly inhibits virus accumulation in the supernatant of HepAD38 cells at 25 nM to 100 nM (P<0.02)[2].

Virus titers have increased 83.5-fold in mice treated with 3.75 mg/kg per day of Morphothiadin, 28.3-fold among mice treated with 7.5 mg/kg per day, but only 3- to 6-fold among mice treated with the higher doses of Morphothiadin. There is generally an inverse relationship between Morphothiadin dose and virus titer, with the greatest rebound seen in mice treated with 3.75 mg/kg per day of Morphothiadin (540-fold) and the smallest rebound in mice treated with 60 mg/kg per day (23-fold) (P<0.001). The Morphothiadin doses of >7.5 mg/kg per day significantly suppresses the virus replication cycle throughout the treatment period, while Morphothiadin doses of >15 mg/kg per day suppresses virus for up to 2 weeks after the end of treatment[2].