Yunjeong Kim, Kyeong-Ok Chang
Feb 15, 2018
Citations
1
Influential Citations
7
Citations
Quality indicators
Journal
Antiviral Research
Abstract
ABSTRACT Feline calicivirus (FCV) is a small non‐enveloped virus containing a single‐stranded, positive‐sense RNA genome of approximately 7.7 kb. FCV is a highly infectious pathogen of cats and typically causes moderate, self‐limiting acute oral and upper respiratory tract diseases or chronic oral diseases. In addition, in recent years, virulent, systemic FCV (vs‐FCV) strains causing severe systemic diseases with a high mortality rate of up to 67% have been reported in cats. Although FCV vaccines are commercially available, their efficacy is limited due to antigenic diversity of FCV strains and short duration of immunity. In this study, we identified fexaramine as a potent inhibitor of FCV including vs‐FCV strains in cell culture and demonstrated that fexaramine is a entry blocker for FCV by using various experiments including time‐of‐addition studies, generation of resistant viruses in cell culture and the reverse genetics system. A fexaramine resistant FCV mutant has a single amino acid change in the P2 domain of VP1 (the major capsid), and the importance of this mutation for conferring resistance was confirmed using the reverse genetics system. A comparative analysis of viral resistance was also performed using a peptidyl inhibitor (NPI52) targeting FCV 3C‐like protease. Finally, the effects of combination treatment of fexaramine and NPI52 against FCV replication and emergence of resistant viruses were investigated in cell culture. HighlightsFexaramine inhibits the replication of feline calicivirus in cells as an entry blocker.A single mutation in the capsid protein of FCV confers resistance to fexaramine.Combined treatment of fexaramine and a viral protease inhibitor substantially delays the emergence of virus resistance.