W15-020 and W16-022 Establishing an in vitro assay for evaluating compounds with activity against feline coronavirus (Winn funded studies); Combined Final Progress Reports
Principal Investigators: Drs. Brian Murphy and Niels C. Pedersen; University of California-Davis
We know how devastating FIP is, but studying the virus causing the disease has been difficult as the virus is difficult to propagate in the laboratory. These investigators funded by Winn Feline Foundation have developed a protocol for growing the virus and studying its susceptibility to a variety of antiviral compounds. They first created ideal conditions necessary to grow the virus optimally in cell culture.
They then experimented with a variety of compounds in order to assess usefulness of each as an antiviral drug for feline coronavirus. Four of the compounds they tested had robust antiviral effects in cell culture. They next assessed the safety of these compounds to cells in culture, with promising results. This work may lead to effective antiviral therapy for feline coronavirus. In a separate study not funded by Winn Feline Foundation, one drug, GC376 has recently undergone efficacy testing in naturally FIP- infected cats.
The researchers also pursued goals that may shed light on the pathogenesis of this virus. They successfully cloned and expressed a vital enzyme of the virus. Inhibition of this enzyme would result in the complete abrogation of virus replication. This is an important first step in designing effective antiviral drugs that target this enzyme.
The net result of these two research studies has been two fold: i) the identification of several noncytotoxic nucleoside analogs that operate as coronaviral polymerase inhibitors, and ii) the cloning and production of the viral polymerase. They are confident that these achievements will facilitate an improved pharmacologic attack in FIP-infected cats. A manuscript describing these achievements is in preparation by the primary investigators. (MK)
Kim Y, Liu H, Kankanamalage AC, et al. Reversal of the progression of fatal coronavirus infection in cats by a broad-spectrum coronavirus protease inhibitor. PLoS Pathog. 2016 May 11;12(5).