2. Academic Validation
  3. GS-441524 inhibits African swine fever virus infection in vitro

GS-441524 inhibits African swine fever virus infection in vitro

  • Antiviral Res. 2021 Jul:191:105081. doi: 10.1016/j.antiviral.2021.105081.
Zhao Huang 1,  Lang Gong 2,  Zezhong Zheng 3,  Qi Gao 4,  Xiongnan Chen 5,  Yang Chen 6,  Xiaojun Chen 7,  Runda Xu 8,  Jiachen Zheng 9,  Zhiying Xu 10,  Shengxun Zhang 11,  Heng Wang 12,  Guihong Zhang 13
Affiliations

Affiliations

  • 1 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. Electronic address: [email protected].
  • 2 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. Electronic address: [email protected].
  • 3 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. Electronic address: [email protected].
  • 4 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. Electronic address: [email protected].
  • 5 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. Electronic address: [email protected].
  • 6 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. Electronic address: [email protected].
  • 7 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. Electronic address: [email protected].
  • 8 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. Electronic address: [email protected].
  • 9 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. Electronic address: [email protected].
  • 10 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. Electronic address: [email protected].
  • 11 Daguang Food Group Co., Ltd., Jiangmen, 529441, China. Electronic address: [email protected].
  • 12 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; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, People's Republic of China. Electronic address: [email protected].
  • 13 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; Research Center for African Swine Fever Prevention and Control, South China Agricultural University, Guangzhou, People's Republic of China; National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China. Electronic address: [email protected].
PMID: 33945807 DOI: 10.1016/j.antiviral.2021.105081
Abstract

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.

Keywords

African swine fever virus; Antiviral; GS-441524; Replication inhibition.

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