Aryamav Pattnaik will present seminar March 25
Aryamav Pattnaik, graduate research assistant in the UNL School of Veterinary Medicine and Biomedical Sciences, will present the seminar "Development of Therapeutics Against Zika Virus," March 25, 2019, in VBS 145 at 4 p.m.
Abstract
Zika virus (ZIKV), a flavivirus was first isolated in 1947 in Uganda. In 2015, re-emergence of ZIKV made major headlines because of its association with congenital defects in human fetuses and an autoimmune disease (Guillain-Barre syndrome) in adults. Several therapeutic approaches against ZIKV have been reported. However, none of them have been approved for clinical use yet. In order to develop therapeutics, we first employed a homology-based approach to predict the structure of ZIKV RNA-dependent RNA polymerase (RDRP). By using the predicted structure, we then conducted in silico screening of a library of 100,000 small molecule compounds and tested the top ten compounds for their ability to inhibit virus replication in in vitro assays. One of the compounds, TPB, efficiently inhibited ZIKV replication at sub-micro molar concentrations and yielded a high selective index of 206. TPB also reduced viremia in immunocompetent mice suggesting its use as a potential drug candidate for ZIKV infections. In another line of investigation to develop a vaccine against ZIKV, we are currently generating a protein-based nanoparticle carrying the envelope (E) protein, the major immunogenic protein of the virus. The protein-based nanoparticle is made from the bacterial ferritin, which is typically assembled into a nanoparticle consisting of 24 molecules. We generated a fusion protein in which the amino-terminal region contained a secretion signal and the soluble portion of the E protein (residues 2-405) fused in-frame with the ferritin molecule. The fusion protein was secreted from the transfected cells. We are currently examining if the fusion protein forms nanoparticles and whether these nanoparticles can be used as a vaccine platform to induce neutralizing antibody response as well as cell-mediated immune responses in animals.
