Back to Search
Start Over
Ursolic acid derivatives are potent inhibitors against porcine reproductive and respiratory syndrome virus
- Source :
- RSC Advances. 10:22783-22796
- Publication Year :
- 2020
- Publisher :
- Royal Society of Chemistry (RSC), 2020.
-
Abstract
- Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating viral pathogens of swine and has a substantial economic impact on the global pork industry. Currently, vaccination strategies provide very limited protection against PRRSV transmission. Therefore, there is an urgent need to develop new antiviral strategies to prevent PRRSV pandemics. In this study, we showed that 3-O-β-chacotriosyl ursolic acid (1) and its ester analogs possessed anti-PRRSV activity in vitro, of which bioisosteric surrogates 7–15 were further generated with the aim of enhancing the selective index. Our results showed that amidation of the 17-COOH group of UA could significantly reduce cytotoxicity and enhance anti-PRRSV activity in MARC-145 cells. Among them, compound 9 displayed the strongest anti-PRRSV activity with the least cytotoxicity. Potent inhibition of representative compounds 9 and 12 on PRRSV infection was observed not only in MARC-145 cells, but also in primary porcine alveolar macrophages, PRRSV-target cells in vivo. Furthermore, compounds 8, 9, 12 and 14 exhibited broad-spectrum inhibitory activities in vitro against high pathogenic type 2 PRRSV NADC30-like and GD-XH strains as well as classical CH-1a and VR2332 strains. Mechanistically, compounds 9 and 12 inhibited PRRSV replication by directly inactivating virions and therefore affecting all tested stages of the virus life cycle, including viral entry, replication and progeny virus release, but did not affect cellular susceptibility to PRRSV. Our findings suggest that compound 9 could be a hit PRRSV inhibitor and deserves further in vivo studies in swine.
- Subjects :
- 0303 health sciences
biology
030306 microbiology
animal diseases
viruses
General Chemical Engineering
virus diseases
General Chemistry
respiratory system
Porcine reproductive and respiratory syndrome virus
biology.organism_classification
Virology
Virus Release
In vitro
03 medical and health sciences
chemistry.chemical_compound
Ursolic acid
chemistry
Viral life cycle
In vivo
Viral entry
Cytotoxicity
030304 developmental biology
Subjects
Details
- ISSN :
- 20462069
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- RSC Advances
- Accession number :
- edsair.doi.dedup.....724f6e6b62a0639c41f3842f926d2552
- Full Text :
- https://doi.org/10.1039/d0ra04070c