US EPA

4238297 

Journal Article 

Potent Inhibitors against Newcastle Disease Virus Hemagglutinin-Neuraminidase 

Review of Transboundary Air Pollution :: RoTAP 

2018 

0 

ChemMedChem
ISSN: 1860-7179
EISSN: 1860-7187 

13 

3 

236-240 

English 

29231283 

10.1002/cmdc.201700755 

WOS:000424514900006 

Neuraminidase activity is essential for the infection and propagation of paramyxoviruses, including human parainfluenza viruses (hPIVs) and the Newcastle disease virus (NDV). Thus, many inhibitors have been developed based on the 2-deoxy-2,3-didehydro-d-N-acetylneuraminic acid inhibitor (DANA) backbone. Along this line, herein we report a series of neuraminidase inhibitors, having C4 (p-toluenesulfonamido and azido substituents) and C5 (N-perfluorinated chains) modifications to the DANA backbone, resulting in compounds with 5- to 15-fold greater potency than the currently most active compound, the N-trifluoroacetyl derivative of DANA (FANA), toward the NDV hemagglutinin-neuraminidase (NDV-HN). Remarkably, these inhibitors were found to be essentially inactive against the human sialidase NEU3, which is present on the outer layer of the cell membrane and is highly affected by the current NDV inhibitor FANA.