Drug screening identified that handelin inhibits feline calicivirus infection by inhibiting HSP70 expression in vitro

Abstract

Feline calicivirus (FCV) is considered one of the major pathogens of cats worldwide and causes upper respiratory tract disease in all cats. In some cats, infection is by a highly virulent strain of FCV (vs.-FCV), which can cause severe and fatal systemic disease symptoms. At present, few antiviral drugs are approved for clinical treatment against FCV. Therefore, there is an imminent need for effective FCV antiviral agents. Here, we used observed a cytopathic effect (CPE) assay to screen 1746 traditional Chinese medicine monomer compounds and found one that can effectively inhibit FCV replication, namely, handelin, with an effective concentration (EC50) value of approximately 2.5 µM. Further study showed that handelin inhibits FCV replication via interference with heat shock protein 70 (HSP70), which is a crucial host factor and plays a positive role in regulating viral replication. Moreover, handelin and HSP70 inhibitors have broad-spectrum antiviral activity. These findings indicate that handelin is a potential candidate for the treatment of FCV infection and that HSP70 may be an important drug target.

Update on feline calicivirus: viral evolution, pathogenesis, epidemiology, prevention and control

“…Nitazoxanide and mizoribine have demonstrated antiviral activity both in vitro and in vivo , suggesting potential therapeutic benefits ( Cui et al, 2020 ). Drug screening has identified handling as an inhibitor of FCV infection through its suppression of HSP70 expression in vitro ( Yan et al, 2024 ). Several antiviral agents, including ribavirin, polysodium 4-styrenesulfonate, mefloquine, and natural compounds, have demonstrated inhibitory effects against FCV replication in vitro ; however, their efficacy in vivo is still uncertain ( Hofmann-Lehmann et al, 2022 ).…”