Identification and characterization of small molecule inhibitors of porcine reproductive and respiratory syndrome virus.
Antiviral Res
; 146: 28-35, 2017 Oct.
Article
in En
| MEDLINE
| ID: mdl-28811186
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Porcine respiratory and reproductive syndrome virus
/
Small Molecule Libraries
/
Drug Discovery
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
Antiviral Res
Year:
2017
Document type:
Article