Abstract

Developing novel antiviral drugs has always been a significant forefront in biological medicine research. Antiviral drugs can be extracted, purified, and synthesized from various biological sources and by different methods. However, they are less explored in veterinary medicine for animal viruses. This research primarily selected feline calicivirus (FCV) to screen the novel antiviral drug against animal viruses. A preliminary screening from a natural product library was conducted, with subsequent assessments to ascertain their toxicity levels and antiviral capabilities. The results showed that decitabine and alprostadil were effective in reducing FCV replication. The decitabine (5-aza-2'-deoxycytidine) was selected for antiviral mechanism investigation. Decitabine has been proven to modulate gene expression through its demethylating effect. Thus, we carried out further experiments and found that decitabine inhibited the FCV by enhancing the transcription of the feline Retinoic acid-inducible gene I (RIG-I) gene. Moreover, we also validated the same antiviral effect and mechanism of decitabine against the canine influenza virus (CIV). In summary, this study unveils the antiviral role of decitabine against FCV and CIV and provides evidence and novel insights into the demethylation drug-mediated antiviral effect for animal RNA viruses.