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Updated: Aug 14, 2026
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Anti-influenza virus activity of peramivir in mice with single intramuscular injection
Shanta Bantia1, C Shane Arnold, Cynthia D Parker
1Department of Biological Sciences, BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive, Birmingham, AL 35244, USA. sbantia@biocryst.com
Abstract:
In the event of an influenza outbreak, antivirals including the neuraminidase (NA) inhibitors, peramivir, oseltamivir, and zanamivir may provide valuable benefit when vaccine production is delayed, limited, or cannot be used. Here we demonstrate the efficacy of a single intramuscular injection of peramivir in the mouse influenza model. Peramivir potently inhibits the neuraminidase enzyme N9 from H1N9 virus in vitro with a 50% inhibitory concentration (IC(50)) of 1.3+/-0.4 nM. On-site dissociation studies indicate that peramivir remains tightly bound to N9 NA (t(1/2)>24h), whereas, zanamivir and oseltamivir carboxylate dissociated rapidly from the enzyme (t(1/2)=1.25 h). A single intramuscular injection of peramivir (10mg/kg) significantly reduces weight loss and mortality in mice infected with influenza A/H1N1, while oseltamivir demonstrates no efficacy by the same treatment regimen. This may be due to tight binding of peramivir to the N1 NA enzymes similar to that observed for N9 enzyme. Additional efficacy studies indicate that a single injection of peramivir (2-20mg/kg) was comparable to a q.d.x 5 day course of orally administered oseltamivir (2-20mg/kg/day) in preventing lethality in H3N2 and H1N1 influenza models. A single intramuscular injection of peramivir may successfully treat influenza infections and provide an alternate option to oseltamivir during an influenza outbreak.
Insights
A single intramuscular injection of peramivir effectively treats influenza in mice by tightly inhibiting the neuraminidase enzyme. This offers a promising alternative to oseltamivir, especially during outbreaks when vaccines are unavailable.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- Neuraminidase (NA) inhibitors like peramivir, oseltamivir, and zanamivir are crucial for treating influenza, particularly when vaccines are limited.
- The efficacy of these antivirals can be influenced by their binding kinetics to the NA enzyme.
Purpose of the Study:
- To evaluate the efficacy of a single intramuscular injection of peramivir in a mouse model of influenza.
- To compare the binding characteristics of peramivir with zanamivir and oseltamivir carboxylate to the NA enzyme.
Main Methods:
- In vitro enzyme inhibition assays to determine the IC(50) of peramivir against N9 NA.
- On-site dissociation studies to assess the binding half-life of peramivir, zanamivir, and oseltamivir carboxylate to N9 NA.
- In vivo efficacy studies in mice infected with influenza A/H1N1, H3N2, and H1N1, comparing single-dose peramivir with oseltamivir treatment.
Main Results:
- Peramivir demonstrated potent inhibition of N9 NA in vitro (IC(50) = 1.3+/-0.4 nM) and exhibited significantly longer binding to the enzyme (t(1/2)>24h) compared to zanamivir and oseltamivir carboxylate (t(1/2)=1.25 h).
- A single intramuscular injection of peramivir (10mg/kg) significantly reduced weight loss and mortality in H1N1-infected mice, whereas oseltamivir showed no efficacy under the same regimen.
- Single peramivir injections (2-20mg/kg) were comparable to a 5-day oral oseltamivir course in preventing lethality in H3N2 and H1N1 models.
Conclusions:
- Peramivir's tight binding to the neuraminidase enzyme contributes to its potent antiviral activity.
- A single intramuscular injection of peramivir is an effective treatment for influenza in mice, offering comparable efficacy to multi-day oseltamivir regimens.
- Peramivir presents a valuable alternative therapeutic option for influenza treatment, especially during outbreaks when vaccine availability is a concern.
