Potent Inhibitors against Newcastle Disease Virus Hemagglutinin‐Neuraminidase |
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| Authors: | Dr. Paola Rota Dr. Paolo La Rocca Dr. Marco Piccoli Dr. Marco Montefiori Dr. Federica Cirillo Prof. Lars Olsen Prof. Marica Orioli Prof. Pietro Allevi Prof. Luigi Anastasia |
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| Affiliation: | 1. Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy;2. Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy;3. Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark;4. Novozymes A/S, Bagsvaerd, Denmark;5. Department of Biomedical Sciences for Health, University of Milan, Segrate, Milan, Italy |
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| Abstract: | 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. |
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| Keywords: | inhibitors NDV neuraminidase sialic acid viruses |
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