1. Academic Validation
  2. Identification and characterization of small molecule inhibitors of porcine reproductive and respiratory syndrome virus

Identification and characterization of small molecule inhibitors of porcine reproductive and respiratory syndrome virus

  • Antiviral Res. 2017 Oct:146:28-35. doi: 10.1016/j.antiviral.2017.08.006.
Alyssa B Evans 1 Pengfei Dong 2 Hyelee Loyd 3 Jianqiang Zhang 4 George A Kraus 5 Susan Carpenter 6
Affiliations

Affiliations

  • 1 Department of Animal Science, Iowa State University, Ames, IA, USA. Electronic address: alyssa.evans@nih.gov.
  • 2 Department of Chemistry, Iowa State University, Ames, IA, USA. Electronic address: pdong@iastate.edu.
  • 3 Department of Animal Science, Iowa State University, Ames, IA, USA. Electronic address: heri1008@iastate.edu.
  • 4 Department of Veterinary Diagnostics and Production Animal Medicine, Iowa State University, Ames, IA, USA. Electronic address: jqzhang@iastate.edu.
  • 5 Department of Chemistry, Iowa State University, Ames, IA, USA. Electronic address: gakraus@iastate.edu.
  • 6 Department of Animal Science, Iowa State University, Ames, IA, USA. Electronic address: scarp@iastate.edu.
Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiological agent of PRRS, an economically significant disease of swine worldwide. PRRSV is poorly controlled by the currently available vaccines, and alternative control strategies are needed to help prevent the continual circulation of the virus. Previously, we developed a synthetic route for the natural compound atractylodinol and demonstrated anti-PRRSV activity in vitro. However, the synthetic route was inefficient and the yield was poor. To identify PRRSV inhibitors that could be synthesized easily and cost-effectively, we synthesized a series of atractylodinol analogs and characterized their anti-PRRSV activity in vitro. A furan-substituted bis-enyne subunit was found to be critical for PRRSV inhibition. Six analogs had potent inhibitory activity against PRRSV with 50% inhibition concentration (IC50) of 0.4-1.4 μM and 50% cytotoxic concentration (CC50) of 209-1537 μM in MARC-145 cells. Three of the most promising compounds also demonstrated significant Antiviral activity and low cytotoxicity in porcine macrophages. Inhibition of PRRSV in MARC-145 cells occurred primarily at a post-entry step during PRRSV replication, between 4 and 12 h post-entry. These results suggest that atractylodinol analogs are promising Antiviral candidates that could augment current PRRSV control strategies.

Keywords

Antivirals; Atractylodinol analogs; PRRSV.

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