Document Type
Article
Journal/Book Title/Conference
Antiviral Chemistry and Chemotherapy
Volume
28
Publisher
Sage Publications Ltd.
Publication Date
8-16-2020
First Page
1
Last Page
5
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Abstract
Clinical evidence suggests that Zika virus contributes to Guillain-Barré syndrome that causes temporary paralysis. We utilized a recently described Zika virus mouse model of temporary flaccid paralysis to address the hypothesis that treatment with an N-methyl-D-aspartate receptor antagonist, memantine, can reduce the incidence of paralysis. Aged interferon alpha/beta-receptor knockout mice were used because of their sublethal susceptibility to Zika virus infection. Fifteen to twenty-five percent of mice infected with a Puerto Rico strain of Zika virus develop acute flaccid paralysis beginning at days 8–9 and peaked at days 10–12. Mice recover from paralysis within a week of onset. In two independent studies, twice daily oral administration of memantine at 60 mg/kg/day on days 4 through 9 after viral challenge significantly reduced the incidence of paralysis. No efficacy was observed with treatments from days 9 through 12. Memantine treatment in cell culture or mice did not affect viral titers. These data indicate that early treatment of memantine before onset of paralysis is efficacious, but treatments beyond the onset of paralysis were not efficacious. The effect of this N-methyl-D-aspartate receptor antagonist on the incidence of Zika virus-induced paralysis may provide guidance for investigations on the mechanism of paralysis.
Recommended Citation
Siddharthan, V., Wang, H., de Oliveira, A. L., Dai, X., & Morrey, J. D. (2020). Memantine treatment reduces the incidence of flaccid paralysis in a zika virus mouse model of temporary paralysis with similarities to Guillain-Barré syndrome. Antiviral Chemistry and Chemotherapy. https://doi.org/10.1177/2040206620950143
