Advertisement

 

 

Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound.

Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound.
Author Information (click to view)

Islam MK, Strand M, Saleeb M, Svensson R, Baranczewski P, Artursson P, Wadell G, Ahlm C, Elofsson M, Evander M,


Islam MK, Strand M, Saleeb M, Svensson R, Baranczewski P, Artursson P, Wadell G, Ahlm C, Elofsson M, Evander M, (click to view)

Islam MK, Strand M, Saleeb M, Svensson R, Baranczewski P, Artursson P, Wadell G, Ahlm C, Elofsson M, Evander M,

Advertisement

Scientific reports 2018 01 318(1) 1925 doi 10.1038/s41598-018-20362-9
Abstract

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.

Submit a Comment

Your email address will not be published. Required fields are marked *

5 × 3 =

[ HIDE/SHOW ]