Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.antiviral.2011.10.002
Title: Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model
Authors: Rathore, A.P.S. 
Paradkar, P.N.
Watanabe, S.
Tan, K.H.
Sung, C.
Connolly, J.E.
Low, J.
Ooi, E.E.
Vasudevan, S.G. 
Keywords: α-Glucosidase inhibitor
AG129 mouse model for dengue infection
Celgosivir
Dengue NS1 protein misfolding
Dengue virus
Issue Date: Dec-2011
Citation: Rathore, A.P.S., Paradkar, P.N., Watanabe, S., Tan, K.H., Sung, C., Connolly, J.E., Low, J., Ooi, E.E., Vasudevan, S.G. (2011-12). Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Antiviral Research 92 (3) : 453-460. ScholarBank@NUS Repository. https://doi.org/10.1016/j.antiviral.2011.10.002
Abstract: Dengue virus (DENV) infections continue to spread aggressively around the world. Here we demonstrate that celgosivir (6-O-butanoyl castanospermine), strongly inhibits all four DENV serotypes. We show by fluorescence microscopy that the antiviral mechanism of celgosivir, is in part, due to misfolding and accumulation of DENV non-structural protein 1 (NS1) in the endoplasmic reticulum. Moreover, celgosivir modulates the host's unfolded protein response (UPR) for its antiviral action. Significantly, celgosivir is effective in lethal challenge mouse models that recapitulate primary or secondary antibody-dependent enhanced DENV infection. Celgosivir treated mice showed enhanced survival, reduced viremia and robust immune response, as reflected by serum cytokine analysis. Importantly, survival increased even after treatment was delayed till 2. days post-infection. Together the present study suggests that celgosivir, which has been clinically determined to be safe in humans, may be a valuable candidate for clinical testing in dengue patients. © 2011 Elsevier B.V.
Source Title: Antiviral Research
URI: http://scholarbank.nus.edu.sg/handle/10635/109957
ISSN: 01663542
DOI: 10.1016/j.antiviral.2011.10.002
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