Tetrandrine (TET) inhibits African swine fever virus entry into cells by blocking the PI3K/Akt pathway

• Published in: Virus research 2024-01, Vol.339, p.199258-199258, Article 199258
• Main Authors: Qian, Bingxu, Hu, Yongxin, Liu, Cong, Zheng, Dongxia, Han, Xiuju, Gong, Mingxia, Zou, Yanli, Zeng, Dexin, Liao, Kai, Miao, Yurun, Wu, Xiaodong, Dai, Jianjun, Wang, Zhiliang, Xue, Feng
• Format: Article
• Language: English
• Subjects: African Swine Fever; African swine fever virus; African Swine Fever Virus - physiology; Animals; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; antiviral properties; Broad-spectrum antiviral drug; Cattle; dose response; Lumpy skin disease virus; Macropinocytosis; Oriental traditional medicine; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt; Porcine epidemic diarrhea virus; Proto-Oncogene Proteins c-akt - metabolism; Stephania; Swine; Tetrandrine; viruses
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2023.199258

•This study revealed the anti-ASFV effect and mechanism of tetrandrine (TET).•The anti-ASFV effect of TET is through inhibition of the PI3K/Akt pathway.•The study demonstrates the broad-spectrum antiviral effect of TET.•It shows potential for broad-spectrum antiviral drugs targeting PI3K/Akt pathway. African Swine Fever Virus (ASFV) infection causes an acute and highly contagious disease in swine, resulting in significant economic losses and societal harm worldwide. Currently, there are no effective vaccines or antiviral drugs available for ASFV. Tetrandrine (TET) is extracted from the traditional Chinese herb Stephania tetrandrae, possesses diverse biological functions such as anti-inflammatory, anti-tumor, and antiviral activities. The study comprehensively evaluated the anti-ASFV effect of TET and validated it through biological assays. The dose-dependent inhibition of TET against ASFV was confirmed and a novel mechanism of TET's anti-ASFV activity was elucidated. TET effectively inhibits ASFV during internalization by blocking macropinocytosis through the inhibition of the PI3K/Akt pathway. The specific inhibitor LY294002, targeting the PI3K/Akt pathway, exhibits similar antiviral activity against ASFV as TET. Furthermore, the inhibitory effect of TET against other viruses such as Lumpy Skin Disease Virus (LSDV) and Porcine Epidemic Diarrhea Virus (PEDV) was also identified. Our findings suggest that TET effectively inhibits ASFV and reveal the potential for broad-spectrum antiviral drugs targeting the PI3K/Akt pathway.