Development of antivirals against Rift Valley fever virus

The purpose of the project is to develop and establish in vivo efficacy for small molecule antivirals against Rift Valley fever virus (RVFV), an emerging mosquito-borne infectious disease with pandemic potential, and a potential biological weapon.Rift Valley fever can severely affect both humans and animals.

There are no human vaccines or specific therapeutics.

Patients cannot be specifically treated and the case-fatally rate can be as high as 30%.We have explored high quality annotated compounds recently made available by pharmaceutical companies in open innovation initiatives.

These compounds are selective and potent against their annotated target, have low or no toxicity, show satisfactory pharmacokinetic profile in vitro and in vivo, and have often proved efficacious in animal models.One host cell target protein emerged as promising for further validation and compounds against this target were potent inhibitors in RVFV cell-based infection assays, and the inhibitors could also block infection of cells by other viruses.To determine the efficacy we will validate the target by using a panel of inhibitor candidates in vitro and then determine the efficacy of the compounds in a lethal mouse model.We expect to identify compounds that are efficacious in vivo and thus strengthen the potential of the candidates for pre-clinical development and eventually human trials.

An anti-RVFV compound with efficacy in vivo will open avenues for further development of new antiviral drugs.