CELGOSIVIR

IC50: 1.27 μM (α-glucosidase I)

Celgosivir is more effective (IC ₅₀ =20 μM) than the parent molecule (IC ₅₀ =254 μM) at causing the accumulation of glucosylated oligosaccharides in HIV-infected cells by inhibition of glycoprotein processing. Celgosivir exhibits potent antiviral activity against HIV-1 with an IC ₅₀ of 2.0±2.3 μM. Bovine viral diarrhoea virus (BVDV) is a closely related virus of hepatitis C virus (HCV). Celgosivir inhibits BVDV with IC ₅₀ values of 16 and 47 μM in plaque assay and cytopathic effect assay, respectively. Celgosivir inhibits DENV2 replication with an EC ₅₀ of 0.2 μM. The EC ₅₀ values against DENV1, 3 and 4 are less than 0.7 μM.

Celgosivir fully protects AG129 mice from lethal infection with a mouse adapted dengue virus at a dose of 50 mg/kg twice daily (BID) for 5 days and is effective even after 48 h delayed treatment. The protection by celgosivir is dose- and schedule-dependent and that a twice-a-day regimen of 50, 25 or 10 mg/kg is more protective than a single daily dose of 100 mg/kg. Pharmacokinetics studies of celgosivir in mice shows that it rapidly metabolizes to castanospermine. During primary infection with a mouse-adapted DENV strain S221, mice shows increased viremia on day 3, yet 80% survived day 10 with virus completely cleared by day 8.