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Anti-Rift Valley fe...
Anti-Rift Valley fever virus activity in vitro , pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound
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Islam, Md. Koushikul (author)
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Strand, Mårten (author)
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Saleeb, Michael (author)
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Svensson, Richard (author)
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Baranczewski, Pawel (author)
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Artursson, Per (author)
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Wadell, Göran (author)
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Ahlm, Clas (author)
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Elofsson, Mikael (author)
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Evander, Magnus (author)
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- NATURE PUBLISHING GROUP 2018
- 2018
- English.
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In: Scientific Reports. - 2045-2322. ; 8
Abstract
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- Rift Valley fever virus (RVFV) is a mosquito-borne hemorrhagic fever virus affecting both humans and animals with severe morbidity and mortality and is classified as a potential bioterror agent due to the possible aerosol transmission. At present there is no human vaccine or antiviral therapy available. Thus, there is a great need to develop new antivirals for treatment of RVFV infections. Benzavir-2 was previously identified as potent inhibitor of human adenovirus, herpes simplex virus type 1, and type 2. Here we assess the anti-RVFV activity of benzavir-2 together with four structural analogs and determine pre-clinical pharmacokinetic parameters of benzavir-2. In vitro, benzavir-2 efficiently inhibited RVFV infection, viral RNA production and production of progeny viruses. In vitro, benzavir-2 displayed satisfactory solubility, good permeability and metabolic stability. In mice, benzavir-2 displayed oral bioavailability with adequate maximum serum concentration. Oral administration of benzavir-2 formulated in peanut butter pellets gave high systemic exposure without any observed toxicity in mice. To summarize, our data demonstrated potent anti-RVFV activity of benzavir-2 in vitro together with a promising pre-clinical pharmacokinetic profile. This data support further exploration of the antiviral activity of benzavir-2 in in vivo efficacy models that may lead to further drug development for human use.
Subject headings
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Microbiology in the medical area (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska och farmaceutiska grundvetenskaper (hsv)
- Mikrobiologi inom det medicinska området (hsv)
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Islam, Md. Koush ...
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Strand, Mårten
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Saleeb, Michael
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Svensson, Richar ...
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Baranczewski, Pa ...
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Artursson, Per
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show more...
-
Wadell, Göran
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Ahlm, Clas
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Elofsson, Mikael
-
Evander, Magnus
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show less...
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