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  2. 5-Bromo-2'-deoxyuridine inhibits African swine fever virus (ASFV) replication via interfering viral DNA replication and suppressing the formation of viral factories

5-Bromo-2'-deoxyuridine inhibits African swine fever virus (ASFV) replication via interfering viral DNA replication and suppressing the formation of viral factories

  • Virology. 2024 Sep 12:600:110237. doi: 10.1016/j.virol.2024.110237.
Feixiang Long 1 Weixin Ou 2 Zexin Liu 2 Guanming Su 2 Qisheng Lin 2 Guoming Su 2 Jinyi Liu 2 Jianxin Chen 3 Ding Luo 4
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Guangzhou, 510642, China; College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
  • 2 College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
  • 3 Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Guangzhou, 510642, China; College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China. Electronic address: jxchen@scau.edu.cn.
  • 4 Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, Guangzhou, 510642, China; College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, China; Department of Anesthesiology, The First Affifiliated Hospital of Jinan University, Guangzhou, 510000, China. Electronic address: luoding225@hotmail.com.
Abstract

African swine fever (ASF), caused by ASF virus (ASFV), represents one of the most economically important viral infectious diseases in swine industry worldwide. So far there is no vaccine or Antiviral drug for controlling ASF pandemics. In the present study, we assessed inhibition of six nucleoside analogues against ASFV replication in ex vivo primary porcine alveolar macrophages (PAMs), including the first approved Antiviral drug idoxuridine. Our results showed that, out of the assessed six compounds, 5-Bromo-2'-Deoxyuridine (5-BrdU, an analog of idoxuridine), exhibited the strongest inhibition on the replication of ASFV in PAMs with a 50% inhibitory concentration (IC50) value of 2.9 μM and a low cytotoxicity (CC50 > 270 μM). Moreover, we showed that 5-BrdU interferes with ASFV DNA replication by incorporating into viral replicating DNA molecules as a competitive substrate for deoxythymidine, ultimately inhibiting the formation of ASFV viral factories. Altogether, our findings suggest that 5-BrdU could serve as a promising therapeutic agent for combating ASFV Infection.

Keywords

5-Bromo-2′-Deoxyuridine (5-BrdU); African swine fever virus (ASFV); Anti-ASFV activity; Virus factory.

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