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GS-441524 inhibits African swine fever virus infection in vitro.

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.
AuthorsZhao Huang, Lang Gong, Zezhong Zheng, Qi Gao, Xiongnan Chen, Yang Chen, Xiaojun Chen, Runda Xu, Jiachen Zheng, Zhiying Xu, Shengxun Zhang, Heng Wang, Guihong Zhang
JournalAntiviral research (Antiviral Res) Vol. 191 Pg. 105081 (07 2021) ISSN: 1872-9096 [Electronic] Netherlands
PMID33945807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 Elsevier B.V. All rights reserved.
Chemical References
  • Antiviral Agents
  • GS-441524
  • Adenosine
Topics
  • Adenosine (analogs & derivatives, pharmacology)
  • African Swine Fever (virology)
  • African Swine Fever Virus (drug effects)
  • Animals
  • Antiviral Agents (pharmacology)
  • Chlorocebus aethiops
  • Macrophages, Alveolar (drug effects, virology)
  • Swine
  • Transcription, Genetic (drug effects)
  • Vero Cells
  • Virus Replication (drug effects)

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