Mechanism of Action of Doxycycline in Inhibiting Feline Infectious Peritonitis Virus
Principal Investigator: Gary Whittaker
DESCRIPTION (provided by applicant):
Feline infectious peritonitis (FIP) is a major infectious disease in the cat population, caused by infection with feline coronavirus (FCoV). Antiviral compounds have recently shown highly promising initial responses for FIP; however, further studies are still needed to be performed to confirm their efficacy in the general cat population. Along with improved husbandry and the ongoing need for an effective vaccine, continuing to explore drug treatment options for FIP is imperative in order to eliminate or decrease FCoV-associated morbidity and mortality. In the past there have been reports of FIP cats that were treated with the antibiotic doxycycline with a positive clinical outcome. As a mechanism of action for this effect, we hypothesize that doxycycline has a direct antiviral effect on FCoV infection, acting either via the viral protease or the viral spike protein (or both). We will test our hypothesis using a range of in vitro techniques to provide a solid scientific foundation for the use of doxycycline to treat cats with FIP or showing initial clinical signs of FIP.
We have one specific aim, to evaluate the effect of doxycycline in vitro and to characterize its inhibitory effect on feline coronavirus. Our specific aim is composed of three sub-aims 1) to examine the effects of doxycycline on FCoV infection in cell culture; 2) to determine the effects of doxycycline on the activity of the FCoV protease(s) using biochemical assays; and 3) to determine the effects of doxycycline on the metal binding activity of the FCoV spike protein.