Fangchinoline inhibits the PEDV replication in intestinal epithelial cells via autophagic flux suppression

Weixiao Zhang; Haiyan Shen; Menglu Wang; Xuelei Fan; Songqi Wang; Nile Wuri; Bin Zhang; Haiyan He; Chunhong Zhang; Zhicheng Liu; Ming Liao; Jianfeng Zhang; Yugu Li; Jianmin Zhang

doi:10.3389/fmicb.2023.1164851

Fangchinoline inhibits the PEDV replication in intestinal epithelial cells via autophagic flux suppression

Front Microbiol. 2023 Jul 7:14:1164851. doi: 10.3389/fmicb.2023.1164851. eCollection 2023.

Authors

Weixiao Zhang^#^{1

2}, Haiyan Shen^#^{2

3}, Menglu Wang^{1

2}, Xuelei Fan^{1

2}, Songqi Wang^{1

2}, Nile Wuri^{2

4}, Bin Zhang^{2

4}, Haiyan He^{2

4}, Chunhong Zhang^{2

3}, Zhicheng Liu^{2

3}, Ming Liao^{2

3}, Jianfeng Zhang^{2

3}, Yugu Li¹, Jianmin Zhang¹

Affiliations

¹ College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
² Key Laboratory of Livestock Disease Prevention of Guangdong Province, Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Ministry of Agriculture and Rural Affairs, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, China.
³ Maoming Branch Center of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology, Guangzhou, China.
⁴ College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, China.

^# Contributed equally.

Abstract

Animal and human health are severely threatened by coronaviruses. The enteropathogenic coronavirus, porcine epidemic diarrhea virus (PEDV), is highly contagious, leading to porcine epidemic diarrhea (PED), which causes large economic losses in the world's swine industry. Piglets are not protected from emerging PEDV variants; therefore, new antiviral measures for PED control are urgently required. Herein, the anti-PEDV effects and potential mechanisms of fangchinoline (Fan) were investigated. Fan dose-dependently inhibited a PEDV infection at 24 h post-infection (EC₅₀ value = 0.67 μM). We found that Fan mainly affected the PEDV replication phase but also inhibited PEDV at the attachment and internalization stages of the viral life cycle. Mechanistically, Fan blocked the autophagic flux in PEDV-infected cells by regulating the expression of autophagy-related proteins and changing PEDV virus particles. In summary, Fan inhibits PEDV infection by blocking the autophagic flux in cells. Our findings will help develop new strategies to prevent and treat PEDV infection.

Keywords: antiviral agent; autophagy; fangchinoline; porcine epidemic diarrhea virus; replication.

Grants and funding

This study was supported by grants from the National Key Research and Development Program of China (grant number 2022YFD1800801-02), the Start-up Research Project of Maoming Laboratory [grant number 2021TDQD002], the Independent Research and Development Projects of Maoming Laboratory [grant number 2022KF010], the Special Fund for Scientific Innovation Strategy-construction of High Level Academy of Agriculture Science-Prominent Talents [grant number R2020PY-JC001], the open competition program of top 10 critical priorities of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province [grant number 2022SDZG02], the Science and Technology Planning Project of Guangdong Province, China [grant numbers 2020A1515010950 and 2021A1515011125], and the National Natural Science Foundation of China [grant number 31302101].