Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus

Eyer, Luděk; Šmídková, Markéta; Nencka, Radim; Neča, Jiřı́; Kastl, Tomas; Palus, Martin; Clercq, Erik De; Růžek, Daniel

doi:10.1016/j.antiviral.2016.07.018

Cited by 71 publications

(70 citation statements)

References 30 publications

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“…Slight differences in EC 50 values between assays are expected due to the differing sensitivities inherent to the assays. We found similar EC 50 values for R1479 against other paramyxoviruses as well, indicating that R1479 not only has potent antiviral activity across the Paramyxoviridae , but that the levels of potency documented closely parallel those observed for R1479 against Flaviviruses and a Pneumovirus (Chen et al, 2014; Eyer et al, 2016; Klumpp et al, 2006; Smith et al, 2007; Wang et al, 2015). Also of note, we found that R1479 exhibited an approximate five-fold increase in EC 50 values when tested against viruses in HeLa cells as compared to NCI-H358 cells.…”

supporting

confidence: 65%

4′-Azidocytidine (R1479) inhibits henipaviruses and other paramyxoviruses with high potency

Hotard

Nichol

et al. 2017

Antiviral Research

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The henipaviruses Nipah virus and Hendra virus are highly pathogenic zoonotic paramyxoviruses which have caused fatal outbreaks of encephalitis and respiratory disease in humans. Despite the availability of a licensed equine Hendra virus vaccine and a neutralizing monoclonal antibody shown to be efficacious against henipavirus infections in non-human primates, there remains no approved therapeutics or vaccines for human use. To explore the possibility of developing small-molecule nucleoside inhibitors against henipaviruses, we evaluated the antiviral activity of 4′-azidocytidine (R1479), a drug previously identified to inhibit flaviviruses, against henipaviruses along with other representative members of the family Paramyxoviridae. We observed similar levels of R1479 antiviral activity across the family, regardless of virus genus. Our brief study expands the documented range of viruses susceptible to R1479, and provides the basis for future investigation and development of 4′-modified nucleoside analogs as potential broad-spectrum antiviral therapeutics across both positive and negative-sense RNA virus families.

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supporting

confidence: 65%

4′-Azidocytidine (R1479) inhibits henipaviruses and other paramyxoviruses with high potency

Hotard

Nichol

et al. 2017

Antiviral Research

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“…This result indicates a cell-type-dependent activity of dasabuvir and efavirenz, which may result from differences in drug uptake or metabolic processing by different cell types. We previously observed similar cell-type-dependent activities in case of anti-VBF activities of arbidol, when the antiviral effect was found to be substantial only in HBCA and Vero cells [31], as well as for several nucleoside analogues, whose antiviral effect was studied in PS and UKF-NB-4 cells [32].…”

Section: None Of the Pdb Non-nucleoside Co-crystalized With Flavivirumentioning

confidence: 52%

FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells

et al. 2020

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Vector-borne flaviviruses (VBFs) affect human health worldwide, but no approved drugs are available specifically to treat VBF-associated infections. Here, we performed in silico screening of a library of U.S. Food and Drug Administration-approved antiviral drugs for their interaction with Zika virus proteins. Twelve hit drugs were identified by the docking experiments and tested in cell-based antiviral assay systems. Efavirenz, tipranavir, and dasabuvir at micromolar concentrations were identified to inhibit all VBFs tested; i.e., two representatives of mosquito-borne flaviviruses (Zika and West Nile viruses) and one representative of flaviviruses transmitted by ticks (tick-borne encephalitis virus). The results warrant further research into these drugs, either individually or in combination, as possible pan-flavivirus inhibitors.

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“…7-Deaza-2ʹ-C-methyl adenosine (7DMA), a potent HCV inhibitor, exerted broad-spectrum antiviral effects against WNV, YFV, DENV-2 (REF. 90), TBEV 96 and ZIKV in cell-based assays 97,98 . 7DMA reduced viraemia in AG129 mice infected with DENV or ZIKV 97,99 .…”

Section: Ns5 Polymerase Inhibitorsmentioning

confidence: 99%

“…7DMA reduced viraemia in AG129 mice infected with DENV or ZIKV 97,99 . Another nucleoside inhibitor, 2ʹ-C-methyladenosine (2ʹCMA), was also reported to inhibit ZIKV 98 and TBEV 96 in titre reduction assays, indicating the potential of 2ʹ-C-methylated nucleosides 96,98 .…”

Section: Ns5 Polymerase Inhibitorsmentioning

confidence: 99%

Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond

Boldescu

Behnam

Vasilakis³

et al. 2017

Nat Rev Drug Discov

248

217

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Infections with flaviviruses, such as dengue, West Nile virus, and the recently re-emerging Zika virus are an increasing and probably lasting global risk. This review summarizes and comments on the opportunities for broad-spectrum agents that are active against a range of flaviviruses. Broad-spectrum activity would be particularly desirable as preparatory measure for the next flaviviral epidemic that could emerge from as-yet-unknown or neglected viruses. Potential target sites for broad-spectrum anti-flaviviral compounds include viral proteins and host mechanisms that are exploited by these viruses during entry and replication. A variety of compounds with broad-spectrum antiviral activity have already been identified by target-specific or phenotypic assays. For some other compound classes, broad-spectrum activity can be anticipated because of their mode of action and molecular target(s).

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Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus

Cited by 71 publications

References 30 publications

4′-Azidocytidine (R1479) inhibits henipaviruses and other paramyxoviruses with high potency

4′-Azidocytidine (R1479) inhibits henipaviruses and other paramyxoviruses with high potency

FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells

Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond

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