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Principal Investigator: Alexander Niclas Freiberg
Organization: UNIVERSITY OF TEXAS MED BR GALVESTON
Fiscal Year: 2021
Award: $240,000
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
Nipah and Hendra viruses are recently emerged bat-borne paramyxoviruses (genus Henipavirus) causing severe
encephalitis and respiratory disease in humans with fatality rates ranging from 40-75%. Despite the severe
pathogenicity of these viruses and their pandemic potential, no therapeutics or vaccines are currently approved
for use in humans. Favipiravir (T-705) is a purine analogue antiviral approved for use in Japan against emerging
influenza strains; and several phase 2 and 3 clinical trials are ongoing in the United States and Europe.
Previously, broad-spectrum antiviral activity of favipiravir has been demonstrated against a large number of RNA
viruses, including members of the Paramyxoviridae, Filoviridae, Arenaviridae, and Bunyaviridae families. With
the ongoing COVID-19 pandemic, favipiravir has also been discussed as a potential antiviral drug for treatment
of mild to moderate symptomatic SARS-CoV-2-infected patients and is currently tested in several clinical trials.
We were able to demonstrate that favipiravir has potent antiviral activity against henipaviruses in cell culture with
EC50's in the low micromolar range. Furthermore, we could show that treatment with favipiravir resulted in full
protection of Nipah virus-infected hamsters, suggesting that favipiravir should be further evaluated as an antiviral
treatment option for henipavirus infections. The overall goal of this application is to develop antiviral treatment
options for infections caused by henipaviruses. Our hypothesis is that favipiravir will demonstrate therapeutic
antiviral efficacy against all human pathogenic Nipah virus strains and Hendra virus in a disease-relevant and
widely accepted small animal model, will be efficacious in a post-exposure setting, and interrupt transmission.
To interrogate our driving hypothesis, we propose the following Specific Aims: (1) Optimize the therapeutic
efficacy of favipiravir against henipavirus infection in the Syrian hamster model; and (2) Evaluate if
favipiravir can evoke extinction of Nipah virus through lethal mutagenesis. The proposed studies will
provide fundamental information for the further development of favipiravir as a broad-spectrum antiviral, and
ultimately lead to the development of countermeasures against henipavirus infections.
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Trials><Cricetinae><Data><Development><Disease><Disorder><Dose><Drug Therapy><Encephalitis><Equine Morbillivirus><Europe><Extinction><Extinction (Psychology)><Family><Fatality rate><Federation of Malaya><Filoviridae><Filovirus><Fruit><Gene Transcription><Genetic Transcription><Genetics-Mutagenesis><Goals><Golden Hamsters><Golden Syrian Hamsters><Hamsters><Hamsters Mammals><Hendra><Hendra Virus><Henipavirus><Henipavirus Infections><Human><Human Metapneumovirus><In Vitro><Infection><Interruption><Japan><Laboratories><Lead><Lung><Lung Respiratory System><Lung diseases><Mainland China><Malay Federation><Malaya><Malaysia><Mesocricetus auratus><Modeling><Modern Man><Mutagenesis><Mutagenesis Molecular Biology><NIAID><National Institute of Allergy and Infectious Disease><Nipah Virus><Oral><Orthobunyavirus><Paramyxoviridae><Paramyxovirus><Pathogenicity><Pb element><Pharmacotherapy><Phase 2 Clinical Trials><Phase 3 Clinical Trials><Phase II Clinical Trials><Phase III Clinical 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