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Potent Inhibitors against Newcastle Disease Virus Hemagglutinin‐Neuraminidase
Author(s) -
Rota Paola,
La Rocca Paolo,
Piccoli Marco,
Montefiori Marco,
Cirillo Federica,
Olsen Lars,
Orioli Marica,
Allevi Pietro,
Anastasia Luigi
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700755
Subject(s) - neuraminidase , newcastle disease , virology , virus , sialidase , paramyxoviridae , hemagglutinin (influenza) , potency , biology , chemistry , microbiology and biotechnology , biochemistry , in vitro , viral disease
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.