Huang Zhao, Gong Lang, Zheng Zezhong, Gao Qi, Chen Xiongnan, Chen Yang, Chen Xiaojun, Xu Runda, Zheng Jiachen, Xu Zhiying, Zhang Shengxun, Wang Heng, Zhang Guihong
Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, People's Republic of China.
Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, People's Republic of China.
Antiviral Res. 2021 Jul;191:105081. doi: 10.1016/j.antiviral.2021.105081. Epub 2021 May 1.
African swine fever virus (ASFV) is a highly infectious and lethal swine pathogen that causes serious socio-economic consequences in endemic countries for which no safe and effective vaccine is currently available. GS-441524, a 1-cyano-substituted adenine C-nucleoside ribose analogue, inhibits viral RNA transcription by competing with natural nucleosides (ATP, TTP, CTP, and GTP) and effectively inhibits viral RNA-dependent RNA polymerase activity. However, whether GS-441524 can inhibit the replication of DNA viruses is unknown. In this study, we confirmed that GS-441524 inhibits ASFV infection in porcine alveolar macrophages (PAMs) in a dose-dependent manner; GS-441524 significantly inhibited ASFV replication at different time points after ASFV infection, particularly at the early stages of viral replication. Notably, GS-441524 did not increase the levels of antiviral cytokines or ATP in PAMs. However, an increase in the concentration of natural ATP in PAMs promoted the replication of ASFV and attenuated the inhibitory effect of GS-441524 in a dose-dependent manner. Our results suggest that GS-441524 is an effective antiviral against ASFV.
非洲猪瘟病毒（ASFV）是一种极具传染性和致命性的猪病原体，在流行国家会造成严重的社会经济后果，目前尚无安全有效的疫苗。GS - 441524是一种1 - 氰基取代的腺嘌呤C - 核苷核糖类似物，通过与天然核苷（ATP、TTP、CTP和GTP）竞争来抑制病毒RNA转录，并有效抑制病毒RNA依赖性RNA聚合酶的活性。然而，GS - 441524是否能抑制DNA病毒的复制尚不清楚。在本研究中，我们证实GS - 441524以剂量依赖性方式抑制猪肺泡巨噬细胞（PAMs）中的ASFV感染；GS - 441524在ASFV感染后的不同时间点显著抑制ASFV复制，尤其是在病毒复制的早期阶段。值得注意的是，GS - 441524并未增加PAMs中抗病毒细胞因子或ATP的水平。然而，PAMs中天然ATP浓度的增加促进了ASFV的复制，并以剂量依赖性方式减弱了GS - 441524的抑制作用。我们的结果表明，GS - 441524是一种有效的抗ASFV抗病毒药物。
