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

Author:

Yan Yuanyuan12,Yang Mengfang12,Jiao Yuzhou12,Li Lisha12,Liu Zirui12,Shi Jiale12,Shen Zhou12,Peng Guiqing21ORCID

Affiliation:

1. Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, PR China

2. State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, PR China

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.

Funder

National Natural Science Foundation of China

Science Fund for Distinguished Young Scholars of Hubei Province

Basic and Applied Basic Research Foundation of Guangdong Province

Publisher

Microbiology Society

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