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Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever

Caroline, AL and Powell, DS and Bethel, LM and Oury, TD and Reed, DS and Hartman, AL (2014) Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever. PLoS Neglected Tropical Diseases, 8 (4). ISSN 1935-2727

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Background:Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705), which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV). RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route.Methodology/Principal Findings:Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92%) survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease.Conclusions/Significance:Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug. © 2014 Caroline et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Caroline, AL
Powell, DS
Bethel, LM
Oury, TDtdoury@pitt.eduTDOURY
Reed, DSdsreed@pitt.eduDSREED
Hartman, ALhartman2@pitt.eduHARTMAN2
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 1 January 2014
Date Type: Publication
Journal or Publication Title: PLoS Neglected Tropical Diseases
Volume: 8
Number: 4
DOI or Unique Handle: 10.1371/journal.pntd.0002790
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
School of Medicine > Immunology
School of Medicine > Pathology
Refereed: Yes
ISSN: 1935-2727
Date Deposited: 02 Jul 2014 21:32
Last Modified: 17 Feb 2018 14:55


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