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Updated: Mar 11, 2026

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
Published on: October 30, 2021
Adenosine triphosphate analogs can efficiently inhibit the Zika virus RNA-dependent RNA polymerase
Kamil Hercík1, Jaroslav Kozak1, Michal Šála1
1Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2, 166 10 Prague 6, Czechia.
Abstract:
We describe the expression and purification of an active recombinant Zika virus RNA-dependent RNA polymerase (RdRp). Next, we present the development and optimization of an in vitro assay to measure its activity. We then applied the assay to selected triphosphate analogs and discovered that 2'-C-methylated nucleosides exhibit strong inhibitory activity. Surprisingly, also carbocyclic derivatives with the carbohydrate locked in a North-like conformation as well as a ribonucleotide with a South conformation exhibited strong activity. Our results suggest that the traditional 2'-C-methylated nucleosides pursued in the race for anti-HCV treatment can be superseded by brand new scaffolds in the case of the Zika virus.
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