This research proposal aims to identify compounds that may be used to combat feline coronavirus (FCoV) infectivity and the resulting disease of Feline Infectious Peritonitis (FIP). We plan to capitalize on the significant advances achieved in the last two years in the Arkin lab studying SARS-CoV-2 due to the COVID-19 pandemic-driven focus of the research community and combine this drug discovery platform with the expertise of the Whittaker lab in translating such in vitro findings to cell-based assays and therapeutic leads for use in cats with FIP. In particular, we wish to exploit recently developed methodologies capable of identifying, characterizing, and, most importantly, blocking coronavirus ion channels by applying these drug discovery approaches to a study of FCoV in the Whittaker lab. Importantly, recent in vivo studies have shown that blocking coronavirus's ion channels is a promising approach to curb infectivity.

Our experimental goals are as follows: a) to identify and characterize the viral channels present in FCoV, b) to screen for novel inhibitors of these channels in vitro, using both negative and positive genetic tests, as well as fluorescence-based tests, c) to test lead compounds in cell culture systems, using both type I and type 2 FCoVs, and d) to estimate drug resistance potential.

This project aims to advance combination therapy for FIP, where the use of different drugs acting on distinct targets is critically important to controlling the emergence of antiviral drug resistance.