Identification and characterization of small molecule inhibitors of porcine reproductive and respiratory syndrome virus
| Autor: | Susan Carpenter, George A. Kraus, Alyssa B. Evans, Jianqiang Zhang, Pengfei Dong, Hyelee Loyd |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
DNA Replication Swine viruses animal diseases Protein subunit 030106 microbiology Porcine Reproductive and Respiratory Syndrome Biology Virus Replication Antiviral Agents Virus Cell Line Small Molecule Libraries 03 medical and health sciences Inhibitory Concentration 50 Virology Drug Discovery Cytotoxic T cell Alternative control Animals Porcine respiratory and reproductive syndrome virus Cytotoxicity Furans Pharmacology Natural compound virus diseases respiratory system Porcine reproductive and respiratory syndrome virus biology.organism_classification Small molecule 030104 developmental biology |
| Zdroj: | Antiviral research. 146 |
| ISSN: | 1872-9096 |
| Popis: | 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 (IC 50 ) of 0.4–1.4 μM and 50% cytotoxic concentration (CC 50 ) 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. |
| Databáze: | OpenAIRE |
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