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Fangchinoline Inhibits African Swine Fever Virus Replication by Suppressing the AKT/mTOR/NF-κB Signaling Pathway in Porcine Alveolar Macrophages

文献类型： 外文期刊

作者： Su, Guanming 1 ; Yang, Xiaoqun 1 ; Lin, Qisheng 1 ; Su, Guoming 1 ; Liu, Jinyi 1 ; Huang, Li 3 ; Chen, Weisan 4 ; Wei, Wenkang 5 ; Chen, Jianxin 1 ;

作者机构： 1.Guangdong Prov Key Lab Vet Pharmaceut Dev & Safety, Guangzhou 510642, Peoples R China

2.South China Agr Univ, Coll Vet Med, Guangzhou 510642, Peoples R China

3.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin 150069, Peoples R China

4.La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem & Genet, Melbourne, Vic 3086, Australia

5.Guangdong Acad Agr Sci, Agrobiol Gene Res Ctr, State Key Lab Swine & Poultry Breeding Ind, Guangzhou 510642, Peoples R China

关键词： African swine fever virus (ASFV); fangchinoline (FAN); inhibition; AKT; mTOR; NF-kappa B

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：4.9； 五年影响因子：5.6 ）

ISSN： 1661-6596

年卷期： 2024 年 25 卷 13 期

页码：

收录情况： SCI

摘要： 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 mu M). Mechanistically, the infection of ASFV triggers the AKT/mTOR/NF-kappa B 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.

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