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Anti-Zika Activity of a Library of Synthetic Carbohydrate Receptors.

Authors :
Palanichamy K
Joshi A
Mehmetoglu-Gurbuz T
Bravo MF
Shlain MA
Schiro F
Naeem Y
Garg H
Braunschweig AB
Source :
Journal of medicinal chemistry [J Med Chem] 2019 Apr 25; Vol. 62 (8), pp. 4110-4119. Date of Electronic Publication: 2019 Apr 08.
Publication Year :
2019

Abstract

Zika virus (ZIKV), a mosquito-borne flavivirus, is a global health concern because of its association with severe neurological disorders. Currently, there are no antiviral therapies that have been specifically approved to treat ZIKV, and there is an urgent need to develop effective anti-ZIKV agents. Here, we report anti-ZIKV activity of 16 synthetic carbohydrate receptors (SCRs) that inhibit ZIKV infection in Vero and HeLa cells. Using a ZIKV reporter virus particle-based infection assay, our data demonstrates these SCRs are highly potent with IC <subscript>50</subscript> s as low as 0.16 μM and negligible toxicity at several-fold higher concentrations. Time-of-addition studies showed that these SCRs inhibit the early stages of the virus infection, which is consistent with the proposed mode of action, where the SCRs likely inhibit binding between the virus and cell-surface glycans, thereby preventing viral entry into the cells and, as such, this study demonstrates a potential new strategy against ZIKV.

Details

Language :
English
ISSN :
1520-4804
Volume :
62
Issue :
8
Database :
MEDLINE
Journal :
Journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
30925051
Full Text :
https://doi.org/10.1021/acs.jmedchem.9b00142