PDF(Pubmed)
Abstract：
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 Stephania tetrandra of the family Menispermaceae, significantly inhibits ASFV replication in porcine alveolar macrophages (PAMs) at micromolar concentrations (IC50 = 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.
摘要：
非洲猪瘟(ASF)由非洲猪瘟病毒（ASFV）引起，是最重要的传染病之一，由于缺乏有效的疫苗，导致猪的高发病率和死亡率以及受影响国家的猪肉行业的巨大经济损失。需要开发替代的强大的抗病毒对策，尤其是抗ASFV药物,是最紧迫的。这项研究表明，芳奇洛林(FAN)，一种双苄基异喹啉生物碱，存在于半子科的Stephaniatetrandra的根中，在微摩尔浓度(IC50=1.66µM)下显著抑制猪肺泡巨噬细胞(PAMs)中的ASFV复制。机械上,ASFV感染可触发AKT/mTOR/NF-κB信号通路。FAN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。本研究结果提示AKT/mTOR通路有可能成为对抗ASFV感染的治疗策略,FAN有可能成为对抗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价.
