Reevaluation of the efficacy of favipiravir against rabies virus using in vivo imaging analysis

Yamada, Kentaro; Noguchi, Kazuko; Kimitsuki, Kazunori; Kaimori, Ryo; Saito, Nobuo; Komeno, Takashi; Nakajima, N.; Furuta, Yoshihiko; Nishizono, Akira

doi:10.1016/j.antiviral.2019.104641

Cited by 35 publications

(29 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reduction of viral replication was greater when estimated on the basis of infectious titers than on total viral RNA as previously observed in non-human primates treated with Remdesivir 22 . However, the effective doses of favipiravir were higher than those usually used in rodent models (≈100-400mg/kg/day) 10,12,[23][24][25][26] . This can be correlated with the high favipiravir EC50 found in vitro for SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

“…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%

See 1 more Smart Citation

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

Driouich

Cochin

Lingas

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Driouich

Cochin

Lingas

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Additional, studies of favipiravir showed in vitro inhibition of RABV but no effect on rabies survival in a mouse model [37][38][39]. Recently, in vivo imaging was used to show favipiravir suppressed RABV replication in the periphery, but double or triple the dose was required to suppress replication in the CNS [40]. Another recent study also showed in vitro efficacy but limited effect in vivo of antimicrobial peptides dermaseptins against RABV in a mouse model [41].…”

Section: Discussionmentioning

confidence: 99%

Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro

Smith

Jackson

Morgan

et al. 2020

Viruses

View full text Add to dashboard Cite

Currently, no rabies virus-specific antiviral drugs are available. Ranpirnase has strong antitumor and antiviral properties associated with its ribonuclease activity. TMR-001, a proprietary bulk drug substance solution of ranpirnase, was evaluated against rabies virus in three cell types: mouse neuroblastoma, BSR (baby hamster kidney cells), and bat primary fibroblast cells. When TMR-001 was added to cell monolayers 24 h preinfection, rabies virus release was inhibited for all cell types at three time points postinfection. TMR-001 treatment simultaneous with infection and 24 h postinfection effectively inhibited rabies virus release in the supernatant and cell-to-cell spread with 50% inhibitory concentrations of 0.2–2 nM and 20–600 nM, respectively. TMR-001 was administered at 0.1 mg/kg via intraperitoneal, intramuscular, or intravenous routes to Syrian hamsters beginning 24 h before a lethal rabies virus challenge and continuing once per day for up to 10 days. TMR-001 at this dose, formulation, and route of delivery did not prevent rabies virus transit from the periphery to the central nervous system in this model (n = 32). Further aspects of local controlled delivery of other active formulations or dose concentrations of TMR-001 or ribonuclease analogues should be investigated for this class of drugs as a rabies antiviral therapeutic.

show abstract

“…Favipiravir has shown in vitro effectiveness against the rabies virus (RABV) but is ineffective in vivo, especially after neuroinvasion. Although favipiravir blocked RABV replication at the site of inoculation in mice, it was not effective in the CNS, which means a method for its adequate penetration into the CNS needs to be devised (41). A randomized clinical trial in China comparing the efficacy of favipiravir and umifenovir for moderate symptoms showed that favipiravir is superior to umifenovir, having a higher recovery rate (71.4 vs. 55.9% for favipiravir and umifenovir, respectively; p = 0.0199).…”

Section: Favipiravirmentioning

confidence: 99%

Treatment Options for COVID-19: A Review

et al. 2020

View full text Add to dashboard Cite

Background: The recent COVID-19 pandemic sweeping the globe has caused great concern worldwide. Due to the limited evidence available on the dynamics of the virus and effective treatment options available, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a huge impact in terms of morbidity and mortality. The economic impact is still to be assessed. Aims: The purpose of this article is to review the evidence for the multiple treatment options available, to consider the future of this global pandemic, and to identify some potential options that could revolutionize the treatment of COVID-19. Moreover, this article underscores the sheer importance of repurposing some of the available antiviral and antimicrobial agents that have long been in use so as to have an effective and expeditious response to this widespread pandemic and the need to conduct a multicenter global randomized controlled trial to find an effective single antiviral agent or a cocktail of available antimicrobial agents. Method: We thoroughly searched and reviewed various case reports, retrospective analyses, and in vitro studies published in PubMed, EMBASE, and Google Scholar regarding the treatment options used for SARS-CoV, MERS-CoV, and SARS-CoV-2 since its outbreak in an attempt to highlight treatments with the most promising results. Conclusion: We are currently facing one of the worst pandemics in history. Although SARS-CoV-2 is associated with a lower mortality rate than are SARS-CoV and MERS-CoV, its higher infectivity is making it a far more serious threat. Unfortunately, no vaccine against SARS-CoV-2 or effective drug regimen for COVID-19 currently exists. Drug repurposing of available antiviral agents may provide a respite; moreover, a cocktail of antiviral agents may be helpful in treating this disease. Here, we have highlighted a few available antimicrobial agents that could be very effective in treating COVID-19; indeed, a number of trials are underway to detect and confirm the efficacy of these agents.

show abstract

Reevaluation of the efficacy of favipiravir against rabies virus using in vivo imaging analysis

Cited by 35 publications

References 50 publications

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

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

Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro

Treatment Options for COVID-19: A Review

Contact Info

Product

Resources

About