State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agriculture University, Wuhan, China.
The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China.
Front Cell Infect Microbiol. 2022 Jun 14;12:856711. doi: 10.3389/fcimb.2022.856711. eCollection 2022.
Porcine epidemic diarrhea virus (PEDV) could cause lethal diarrhea and dehydration in suckling piglets, which can adversely affect the development of the global swine industry. The lack of effective therapeutical and prophylactic treatment especially for PEDV variant strains underlines the importance of effective antiviral strategies, such as identification of novel antiviral agents. In the present study, the antiviral activity of cinchonine against PEDV was investigated in Vero CCL81 and LLC-PK1 cells at a non-cytotoxic concentration determined by Cell Counting Kit-8 assay . We found that cinchonine exhibited a significant suppression effect against PEDV infection and its inhibitory action was primarily focused on the early stage of PEDV replication. Moreover, we also observed that cinchonine could significantly induce autophagy by detecting the conversion of LC3-I to LC3-II by using western blot analysis. Cinchonine treatment could inhibit PEDV replication in a dose-dependent manner in Vero CCL81 cells, while this phenomenon disappeared when autophagy was attenuated by pre-treatment with autophagy inhibitor 3MA. Consequently, this study indicated that cinchonine can inhibit PEDV replication inducing cellular autophagy and thus from the basis for successful antiviral strategies which potentially suggest the possibility of exploiting cinchonine as a novel antiviral agent.
猪流行性腹泻病毒(PEDV)可导致仔猪致命性腹泻和脱水,这会对全球养猪业的发展产生不利影响。由于缺乏针对 PEDV 变异株的有效治疗和预防措施,因此强调了采用有效的抗病毒策略的重要性,例如鉴定新型抗病毒药物。在本研究中,通过细胞计数试剂盒-8 法确定的非细胞毒性浓度,在 Vero CCL81 和 LLC-PK1 细胞中研究了金鸡纳碱对 PEDV 的抗病毒活性。我们发现,金鸡纳碱对 PEDV 感染具有显著的抑制作用,其抑制作用主要集中在 PEDV 复制的早期阶段。此外,我们还通过 Western blot 分析检测 LC3-I 向 LC3-II 的转化,观察到金鸡纳碱可以显著诱导自噬。金鸡纳碱处理可以以剂量依赖的方式抑制 Vero CCL81 细胞中的 PEDV 复制,而在用自噬抑制剂 3MA 预先处理以减弱自噬时,这种现象消失。因此,本研究表明,金鸡纳碱可以通过诱导细胞自噬来抑制 PEDV 复制,从而为成功的抗病毒策略奠定了基础,这可能提示了利用金鸡纳碱作为新型抗病毒药物的可能性。