WFRF:(Saleeb Michael)
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- Islam, Md. KoushikulUmeå universitet,Infektionssjukdomar,Umea Univ, Dept Clin Microbiol, Infect Dis, Umea, Sweden. (author)
Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound
- Article/chapterEnglish2018
Publisher, publication year, extent ...
- 2018-01-31
- NATURE PUBLISHING GROUP,2018
- electronicrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:umu-144950
- https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-144950URI
- https://doi.org/10.1038/s41598-018-20362-9DOI
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-346222URI
Supplementary language notes
- Language:English
- Summary in:English
Part of subdatabase
- SwePubSwePub
Classification
Notes
- 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 and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Mikrobiologi inom det medicinska området hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Microbiology in the medical area hsv//eng
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine hsv//eng
Added entries (persons, corporate bodies, meetings, titles ...)
- Strand, MårtenUmeå universitet,Virologi,Umea Univ, Dept Clin Microbiol, Virol, Umea, Sweden.(Swepub:umu)mansnd02 (author)
- Saleeb, MichaelUmeå universitet,Kemiska institutionen,Umea Univ, Dept Chem, Umea, Sweden.(Swepub:umu)misa0058 (author)
- Svensson, RichardUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci,UDOPP(Swepub:uu)ricsv977 (author)
- Baranczewski, PawelUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci,UDOPP(Swepub:uu)pawba132 (author)
- Artursson, PerUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaci,UDOPP(Swepub:uu)perartur (author)
- Wadell, GöranUmeå universitet,Virologi,Umea Univ, Dept Clin Microbiol, Virol, Umea, Sweden.(Swepub:umu)gowa0001 (author)
- Ahlm, ClasUmeå universitet,Infektionssjukdomar,Umea Univ, Dept Clin Microbiol, Infect Dis, Umea, Sweden.(Swepub:umu)clah0001 (author)
- Elofsson, MikaelUmeå universitet,Kemiska institutionen,Umea Univ, Dept Chem, Umea, Sweden.(Swepub:umu)miel0001 (author)
- Evander, MagnusUmeå universitet,Virologi,Umea Univ, Dept Clin Microbiol, Virol, Umea, Sweden.(Swepub:umu)maev0001 (author)
- Umeå universitetInfektionssjukdomar (creator_code:org_t)
Related titles
- In:Scientific Reports: NATURE PUBLISHING GROUP82045-2322
Internet link
- https://doi.org/10.1038/s41598-018-20362-9Fulltext
- https://umu.diva-portal.org/smash/get/diva2:1184906/FULLTEXT01.pdffulltext:print
- https://www.nature.com/articles/s41598-018-20362-9.pdf
- https://uu.diva-portal.org/smash/get/diva2:1191416/FULLTEXT01.pdffulltext:print
- https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-144950
- https://doi.org/10.1038/s41598-018-20362-9
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-346222
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