Flaviviral Infections and Potential Targets for Antiviral Therapy

Baier, Andrea

doi:10.5772/21845

Cited by 10 publications

(7 citation statements)

References 72 publications

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“…Despite similarities in genomic organization, replication strategy, and physicochemical properties, flaviviruses can cause a variety of diseases with clinical presentations ranging from mild fever to hemorrhagic fever, encephalitis, Guillain-Barré syndrome, and microcephaly [2]. Important human pathogens include yellow fever virus, dengue virus, West Nile virus (WNV), Zika virus (ZIKV), Japanese encephalitis virus, and tick-borne encephalitis virus (TBEV) [3,4]. No approved effective antiviral therapy directed against these viruses is currently available.…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…T ick-borne encephalitis virus (TBEV) belongs to the Flaviviridae family, which includes other human-and animal-pathogenic viruses of global importance, such as West Nile virus (WNV), dengue virus (DENV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), and hepatitis C virus (HCV) (1). TBEV virions are approximately 50 nm in diameter and are composed of a spherical nucleocapsid surrounded by a host-derived lipid bilayer.…”

mentioning

confidence: 99%

Nucleoside Inhibitors of Tick-Borne Encephalitis Virus

Eyer

Valdés

Gil

et al. 2015

Antimicrob Agents Chemother

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The anti-TBEV effect of 2=-CMA in cell culture diminished gradually after day 3 posttreatment. 7-Deaza-2=-CMA showed no detectable cellular toxicity (CC 50 > 50 M), and the antiviral effect in culture was stable for >6 days posttreatment. Computational molecular analyses revealed that compared to the other two compounds, 7-deaza-2=-CMA formed a large cluster near the active site of the TBEV polymerase. High antiviral activity and low cytotoxicity suggest that 7-deaza-2=-CMA is a promising candidate for further investigation as a potential therapeutic agent in treating TBEV infection.

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“…West Nile virus (WNV) is an emerging representative of the genus Flavivirus 46 belonging to the family Flaviviridae. This family also includes other medically important 47 human pathogens, such as Dengue virus (DENV), Japanese encephalitis virus (JEV), yellow 48 fever virus (YFV), Zika virus (ZIKV), and tick-borne encephalitis virus (TBEV) (1). WNV has 49 been serologically classified into the JEV antigenic complex and divided into eight genotypic 50 lineages; from a medical point of view, the strains pathogenic for humans are designated as 51 lineages 1 and 2 (2).…”

Section: Introduction 45mentioning

confidence: 99%

Viral RNA-dependent RNA polymerase inhibitor 7-deaza-2′-C-methyladenosine prevents death in a mouse model of West Nile virus infection

Eyer

Fojtíková

Nencka

et al. 2018

Preprint

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24West Nile virus (WNV) is a medically important emerging arbovirus causing serious 25 neuroinfections in humans against which no approved antiviral therapy is currently available. 26In this study, we demonstrate that 2´-C-methyl-or 4´-azido-modified nucleosides are highly 27 effective inhibitors of WNV replication, showing nanomolar or low micromolar anti-WNV 28 activity and negligible cytotoxicity in cell culture. One representative of C2´-methylated 29 nucleosides, 7-deaza-2´-C-methyladenosine, significantly protected WNV-infected mice from 30 disease progression and mortality. Twice daily treatment at 25 mg/kg starting at the time of 31 infection resulted in 100% survival of the mice. This compound was highly effective, even if 32 the treatment was initiated 3 days post-infection, at the time of a peak of viremia, which 33 resulted in a 90% survival rate. However, the antiviral effect of 7-deaza-2´-C-34 methyladenosine was absent or negligible when the treatment was started 8 days post-35 infection (i.e., at the time of extensive brain infection). The 4´-azido moiety appears to be 36 another important determinant for highly efficient inhibition of WNV replication in vitro. 37However, the strong anti-WNV effect of 4´-azidocytidine and 4´-azido-aracytidine was cell 38 type-dependent and observed predominantly in PS cells. The effect was much less 39 pronounced in Vero cells. Our results indicate that 2´-C-methylated or 4´-azidated 40 nucleosides merit further investigation as potential therapeutic agents for treating WNV 41 infections, as well as infections caused by other medically important flaviviruses. 42 43 44

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Flaviviral Infections and Potential Targets for Antiviral Therapy

Cited by 10 publications

References 72 publications

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

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

Nucleoside Inhibitors of Tick-Borne Encephalitis Virus

Viral RNA-dependent RNA polymerase inhibitor 7-deaza-2′-C-methyladenosine prevents death in a mouse model of West Nile virus infection

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