Liu Yuanjia, Zhang Xinheng, Liu Zexin, Huang Li, Jia Weixin, Lian Xinlei, Weng Changjiang, Zhang Guihong, Qi Wenbao, Chen Jianxin
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
College of Animal Science, South China Agricultural University, Guangzhou, China.
Front Microbiol. 2022 Aug 30;13:970501. doi: 10.3389/fmicb.2022.970501. eCollection 2022.
African swine fever virus (ASFV) is a highly infectious and lethal swine pathogen that causes severe socio-economic consequences in affected countries. Unfortunately, effective vaccine for combating ASF is unavailable so far, and the prevention and control strategies for ASFV are still very limited. Toosendanin (TSN), a triterpenoid saponin extracted from the medicinal herb Sieb. Et Zucc, has been demonstrated to possess analgesic, anti-inflammatory, anti-botulism and anti-microbial activities, and was used clinically as an anthelmintic, while the antiviral effect of TSN on ASFV has not been reported. In this study, we revealed that TSN exhibited a potent inhibitory effect on ASFV GZ201801-38 strain in porcine alveolar macrophages (PAMs; EC = 0.085 μM, SI = 365) in a dose-dependent manner. TSN showed robust antiviral activity in different doses of ASFV infection and reduced the transcription and translation levels of ASFV p30 protein, viral genomic DNA quantity as well as viral titer at 24 and 48 h post-infection. In addition, TSN did not affect virion attachment and release but intervened in its internalization in PAMs. Further investigations disclosed that TSN played its antiviral role by upregulating the host IFN-stimulated gene (ISG) IRF1 rather than by directly inactivating the virus particles. Overall, our results suggest that TSN is an effective antiviral agent against ASFV replication and may have the potential for clinical use.
非洲猪瘟病毒（ASFV）是一种极具传染性和致死性的猪病原体，在受影响国家会造成严重的社会经济后果。不幸的是，目前尚无有效的抗非洲猪瘟疫苗，且针对ASFV的防控策略仍然非常有限。川楝素（TSN）是从中药材川楝（Sieb. Et Zucc）中提取的一种三萜皂苷，已被证明具有镇痛、抗炎、抗肉毒杆菌和抗菌活性，并在临床上用作驱虫药，然而TSN对ASFV的抗病毒作用尚未见报道。在本研究中，我们发现TSN对猪肺泡巨噬细胞（PAMs）中的ASFV GZ201801 - 38株具有显著的抑制作用（EC = 0.085 μM，SI = 365），且呈剂量依赖性。TSN在不同剂量的ASFV感染中均表现出强大的抗病毒活性，并在感染后24小时和48小时降低了ASFV p30蛋白的转录和翻译水平、病毒基因组DNA数量以及病毒滴度。此外，TSN不影响病毒粒子的附着和释放，但干预其在PAMs中的内化过程。进一步研究表明，TSN通过上调宿主干扰素刺激基因（ISG）IRF1发挥其抗病毒作用，而非直接使病毒粒子失活。总体而言，我们的结果表明TSN是一种有效的抗ASFV复制抗病毒剂，可能具有临床应用潜力。
