Cell experiment:

The cytotoxicity of Celgosivir is measured by the Cell titer-Glo Luminescent cell viability assay. The luminescence signals for cells treated with the test compounds are compared to those for cells treated with the maximum tolerated DMSO to determine the 50% cytotoxic concentration[3].

Animal experiment:

Mice: To model ADE, mice are injected i.p. with 20 μg /mouse of mouse monoclonal antibody against DENV E protein one day prior to infection. For treatment during infection, celgosivir (50 mg/kg) is injected i.p. twice daily for 5 days, starting from day 0, 1 or 2. Blood is collected at days 1, 3 and 7 by submandibular bleeding. Survival of mice is followed until day 10 and survival curves are plotted[3].

Celgosivir (MBI 3253; MDL 28574; MX3253) is a novel α-glucosidase I inhibitor, an enzyme that plays a critical role in viral maturation by initiating the processing of the N-linked oligosaccharides of viral envelope glycoproteins.[1]

The quantity of THP-1 cells is 1 × 105 , cells were washed once with media and replaced with 500 μl with a serial 4-fold dilution starting from 200 μM or 50 μM.[3]

Celgosivir, stored at 100 mg/ml in PBS at 30 °C, were diluted with PBS before each dosing to obtain 1 mg/200 μl (50 mg/kg) or 0.2 mg/200 μl (10 mg/kg). [3]

[1]. Durantel D. Celgosivir, an alpha-glucosidase I inhibitor for the potential treatment of HCV infection. Curr Opin Investig Drugs. 2009 Aug, 10(8):860-70. [2]. Whitby K et al. Action of celgosivir (6 O-butanoyl castanospermine) against the pestivirus BVDV: implications for thetreatment of hepatitis C. Antivir Chem Chemother, 2004 May, 15(3):141-51. [3]. Satoru Watanabe，Kitti Wing-Ki Chan et al. Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy. Antiviral Research, March 2016, Pages 10-19.