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Anti-Zika Activity of a Library of Synthetic Carbohydrate Receptors.
- 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.
- Subjects :
- Animals
Antiviral Agents pharmacology
Antiviral Agents therapeutic use
Cell Survival drug effects
Chlorocebus aethiops
HeLa Cells
Humans
Receptors, Artificial chemical synthesis
Receptors, Artificial metabolism
Structure-Activity Relationship
Suramin chemistry
Suramin pharmacology
Vero Cells
Virus Internalization drug effects
Zika Virus Infection drug therapy
Zika Virus Infection pathology
Antiviral Agents chemistry
Carbohydrates chemistry
Receptors, Artificial chemistry
Zika Virus physiology
Subjects
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