Favipiravir inhibits in vitro Usutu virus replication and delays disease progression in an infection model in mice

Segura, Nidya Alexandra; Sharma, Sapna; Neyts, Johan; Kaptein, Suzanne

doi:10.1016/j.antiviral.2018.10.026

Cited by 26 publications

(32 citation statements)

References 44 publications

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“…Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamine) is an anti-influenza drug approved in Japan that has shown broad-spectrum antiviral activity against a variety of other RNA viruses [9][10][11][12][13][14][15] . Favipiravir is a prodrug that is metabolized intracellularly into its active ribonucleoside 5'-triphosphate form that acts as a nucleotide analogue to selectively inhibit RNA-dependent RNA polymerase and induce lethal mutagenesis 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

Driouich

Cochin

Lingas

et al. 2020

Preprint

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SummaryThere is a need for safe and effective antiviral molecules with which to combat COVID-19 pandemics. Recently, in vitro inhibitory activity of favipiravir against SARS-CoV-2 was reported. Here, we used a Syrian hamster model to explore the pharmacokinetics of this molecule and its in vivo efficacy against SARS-CoV-2. Results revealed that high doses (700-1400mg/kg/day) significantly reduced virus replication in the lungs accompanied by clinical alleviation of the disease. However, these high doses were associated with significant toxicity in hamsters. Favipiravir pharmacokinetics displayed non-linear increase in plasma exposure between the doses and good lung penetration. Analysis of viral genomes in vivo showed that favipiravir induced a mutagenic effect. Whilst the plasma trough concentrations observed in this study were comparable with those previously found during human clinical trials, this potential toxicity requires further investigation to assess whether a tolerable dosing regimen can be found in humans that effectively reduces virus replication.

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Section: Introductionmentioning

confidence: 99%

Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

Driouich

Cochin

Lingas

et al. 2020

Preprint

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“…One of the reasons for the resistance of immunocompetent mice is the IFN response that plays a major role in the control of the in vivo pathogenesis of USUV, as well as other flaviviruses such as Zika virus [28]. In fact, contrary to immunocompetent mice, high mortality rates were observed after USUV infection in suckling mice (which have not yet developed a functional IFN response [21,25]), or in mice knocked-out for the IFN-α/β and/or IFN-γ pathways [23,27]. Nonetheless, our study could illustrate the neuroinvasiveness and neurovirulence of USUV in an immunocompetent mouse injected via the i.d.…”

Section: Discussionmentioning

confidence: 99%

“…reflects both neurovirulence and neuroinvasiveness [26]. Thus, researchers have capitalized on the ability of suckling mice [21,25] or mice lacking the interferon α/β receptor (IFNAR-/-) [23,27] to model USUV neuroinvasiveness and neuropathogenicity [25] and to test the effect of some antiviral [27] and vaccine [23] candidates. However, the lack of a fully functional immune response in these animals hinders their ability to accurately model disease pathogenesis and to investigate the efficacy of certain vaccine candidates [28].…”

Section: Introductionmentioning

confidence: 99%

New Insights into the Susceptibility of Immunocompetent Mice to Usutu Virus

Benzarti

Sarlet

Franssen

et al. 2020

Viruses

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Usutu virus (USUV) is a mosquito-borne flavivirus that shares many similarities with the closely related West Nile virus (WNV) in terms of ecology and clinical manifestations. Initially distributed in Africa, USUV emerged in Italy in 1996 and managed to co-circulate with WNV in many European countries in a similar mosquito–bird life cycle. The rapid geographic spread of USUV, the seasonal mass mortalities it causes in the European avifauna, and the increasing number of infections with neurological disease both in healthy and immunocompromised humans has stimulated interest in infection studies to delineate USUV pathogenesis. Here, we assessed the pathogenicity of two USUV isolates from a recent Belgian outbreak in immunocompetent mice. The intradermal injection of USUV gave rise to disorientation and paraplegia and was associated with neuronal death in the brain and spinal cord in a single mouse. Intranasal inoculation of USUV could also establish the infection; viral RNA was detected in the brain 15 days post-infection. Overall, this pilot study probes the suitability of this murine model for the study of USUV neuroinvasiveness and the possibility of direct transmission in mammals.

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“…Sofosbuvir was initially developed and approved by FDA for treatment of hepatitis C. It shows activity against a number of flaviviruses in vitro and in the mouse model [33,105]. Further interesting candidates (13 compounds listed in Table 1) inhibit the viral polymerase [39,128]), NS2B/NS3 protease and kinases [23,24]), cell entry and membrane trafficking [20,109], and other flavivirus targets. The action and the efficacy of most of these compounds in vivo are yet to be determined.…”

Section: Flaviviridaementioning

confidence: 99%

“…Broad-spectrum antivirals on the other hand show significant activity against several members of the same or distinct virus families, allowing the empirical treatment of severe viral infections prior to positive diagnosis of the viral agent. Leading examples are at his point the pyrazinecarboxamide compounds T-705 (favipiravir; [2,7,48]), T-1105 and T-1106, which are broad-spectrum viral RNA polymerase inhibitors, initially developed for the treatment of influenza virus, and found effective against bunyaviruses [21,54,59], alphaviruses [1], filoviruses [13] arenaviruses [125], paramyxoviruses [29], and flaviviruses [128]. A favipiravir resistance mechanism in influenza virus has been described [52].…”

Section: Synergy Through Combination and The Use Of Broad-spectrum Anmentioning

confidence: 99%

Antivirals in medical biodefense

et al. 2020

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The viruses historically implicated or currently considered as candidates for misuse in bioterrorist events are poxviruses, filoviruses, bunyaviruses, orthomyxoviruses, paramyxoviruses and a number of arboviruses causing encephalitis, including alpha-and flaviviruses. All these viruses are of concern for public health services when they occur in natural outbreaks or emerge in unvaccinated populations. Recent events and intelligence reports point to a growing risk of dangerous biological agents being used for nefarious purposes. Public health responses effective in natural outbreaks of infectious disease may not be sufficient to deal with the severe consequences of a deliberate release of such agents. One important aspect of countermeasures against viral biothreat agents are the antiviral treatment options available for use in post-exposure prophylaxis. These issues were adressed by the organizers of the 16th Medical Biodefense Conference, held in Munich in 2018, in a special session on the development of drugs to treat infections with viruses currently perceived as a threat to societies or associated with a potential for misuse as biothreat agents. This review will outline the state-of-the-art methods in antivirals research discussed and provide an overview of antiviral compounds in the pipeline that are already approved for use or still under development.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Favipiravir inhibits in vitro Usutu virus replication and delays disease progression in an infection model in mice

Cited by 26 publications

References 44 publications

Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

New Insights into the Susceptibility of Immunocompetent Mice to Usutu Virus

Antivirals in medical biodefense

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