Broad-Spectrum Antiviral Activity of 39-Deoxy-39-Fluoroadenosine against Emerging Flaviviruses
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F21%3AN0000111" target="_blank" >RIV/00027162:_____/21:N0000111 - isvavai.cz</a>
Result on the web
<a href="https://journals.asm.org/doi/full/10.1128/AAC.01522-20" target="_blank" >https://journals.asm.org/doi/full/10.1128/AAC.01522-20</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1128/AAC.01522-20" target="_blank" >10.1128/AAC.01522-20</a>
Alternative languages
Result language
angličtina
Original language name
Broad-Spectrum Antiviral Activity of 39-Deoxy-39-Fluoroadenosine against Emerging Flaviviruses
Original language description
Emerging flaviviruses are causative agents of severe and life-threatening diseases, against which no approved therapies are available. Among the nucleoside analogues, which represent a promising group of potentially therapeutic compounds, fluorine-substituted nucleosides are characterized by unique structural and functional properties. Despite having first been synthesized almost 5 decades ago, they still offer new therapeutic opportunities as inhibitors of essential viral or cellular enzymes active in nucleic acid replication/transcription or nucleoside/nucleotide metabolism. Here, we report evaluation of the antiflaviviral activity of 28 nucleoside analogues, each modified with a fluoro substituent at different positions of the ribose ring and/or heterocyclic nucleobase. Our antiviral screening revealed that 3′-deoxy-3′-fluoroadenosine exerted a low-micromolar antiviral effect against tick-borne encephalitis virus (TBEV), Zika virus, and West Nile virus (WNV) (EC50 values from 1.1 ± 0.1 μM to 4.7 ± 1.5 μM), which was manifested in host cell lines of neural and extraneural origin. The compound did not display any measurable cytotoxicity up to concentrations of 25 μM but had an observable cytostatic effect, resulting in suppression of cell proliferation at concentrations of >12.5 μM. Novel approaches based on quantitative phase imaging using holographic microscopy were developed for advanced characterization of antiviral and cytotoxic profiles of 3′-deoxy-3′-fluoroadenosine in vitro. In addition to its antiviral activity in cell cultures, 3′-deoxy-3′-fluoroadenosine was active in vivo in mouse models of TBEV and WNV infection. Our results demonstrate that fluoro-modified nucleosides represent a group of bioactive molecules with excellent potential to serve as prospective broad-spectrum antivirals in antiviral research and drug development.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10607 - Virology
Result continuities
Project
<a href="/en/project/LTAUSA18016" target="_blank" >LTAUSA18016: Search for novel nucleoside analogs as antivirals against medically important flaviviruses.</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN
0066-4804
e-ISSN
1098-6596
Volume of the periodical
65
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
19
Pages from-to
"e01522-20"
UT code for WoS article
000609954100018
EID of the result in the Scopus database
2-s2.0-85099983413