Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Guangzhou 510642, China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Int J Mol Sci. 2024 Jun 29;25(13):7178. doi: 10.3390/ijms25137178.
African swine fever (ASF), caused by the African swine fever virus (ASFV), is one of the most important infectious diseases that cause high morbidity and mortality in pigs and substantial economic losses to the pork industry of affected countries due to the lack of effective vaccines. The need to develop alternative robust antiviral countermeasures, especially anti-ASFV agents, is of the utmost urgency. This study shows that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid found in the roots of of the family Menispermaceae, significantly inhibits ASFV replication in porcine alveolar macrophages (PAMs) at micromolar concentrations (IC = 1.66 µM). Mechanistically, the infection of ASFV triggers the AKT/mTOR/NF-κB signaling pathway. FAN significantly inhibits ASFV-induced activation of such pathways, thereby suppressing viral replication. Such a mechanism was confirmed using an AKT inhibitor MK2206 as it inhibited AKT phosphorylation and ASFV replication in PAMs. Altogether, the results suggest that the AKT/mTOR pathway could potentially serve as a treatment strategy for combating ASFV infection and that FAN could potentially emerge as an effective novel antiviral agent against ASFV infections and deserves further in vivo antiviral evaluations.
非洲猪瘟（ASF）由非洲猪瘟病毒（ASFV）引起，是一种最重要的传染病之一，由于缺乏有效的疫苗，它可导致猪的高发病率和死亡率，并给受影响国家的猪肉产业造成巨大的经济损失。因此，迫切需要开发替代的强大抗病毒对策，特别是抗 ASFV 药物。本研究表明，在根中发现的双苄基异喹啉生物碱防己诺林碱（FAN）在毫摩尔浓度下（IC = 1.66 µM）可显著抑制猪肺泡巨噬细胞（PAMs）中的 ASFV 复制。从机制上讲，ASFV 的感染会触发 AKT/mTOR/NF-κB 信号通路。FAN 可显著抑制 ASFV 诱导的这些途径的激活，从而抑制病毒复制。使用 AKT 抑制剂 MK2206 证实了这种机制，因为它抑制了 PAMs 中的 AKT 磷酸化和 ASFV 复制。总而言之，结果表明 AKT/mTOR 途径可能成为对抗 ASFV 感染的治疗策略，而 FAN 可能成为对抗 ASFV 感染的有效新型抗病毒药物，值得进一步进行体内抗病毒评估。
