Potent Inhibitors against Newcastle Disease Virus Hemagglutinin-Neuraminidase

Paola Rota; Paolo La Rocca; Marco Piccoli; Marco Montefiori; Federica Cirillo; Lars Olsen; Marica Orioli; Pietro Allevi; Luigi Anastasia

doi:10.1002/cmdc.201700755

Potent Inhibitors against Newcastle Disease Virus Hemagglutinin-Neuraminidase

Paola Rota^*, Paolo La Rocca, Marco Piccoli, Marco Montefiori, Federica Cirillo, Lars Olsen, Marica Orioli, Pietro Allevi, Luigi Anastasia

^*Corresponding author af dette arbejde

6 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	ChemMedChem
Vol/bind	13
Udgave nummer	3
Sider (fra-til)	236-240
Antal sider	5
ISSN	1860-7179
DOI	https://doi.org/10.1002/cmdc.201700755
Status	Udgivet - 6 feb. 2018

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10.1002/cmdc.201700755

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Citationsformater

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title = "Potent Inhibitors against Newcastle Disease Virus Hemagglutinin-Neuraminidase",

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.",

author = "Paola Rota and Paolo La Rocca and Marco Piccoli and Marco Montefiori and Federica Cirillo and Lars Olsen and Marica Orioli and Pietro Allevi and Luigi Anastasia",

year = "2018",

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language = "English",

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T1 - Potent Inhibitors against Newcastle Disease Virus Hemagglutinin-Neuraminidase

AU - Rota, Paola

AU - La Rocca, Paolo

AU - Piccoli, Marco

AU - Montefiori, Marco

AU - Cirillo, Federica

AU - Olsen, Lars

AU - Orioli, Marica

AU - Allevi, Pietro

AU - Anastasia, Luigi

PY - 2018/2/6

Y1 - 2018/2/6

N2 - 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.

AB - 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.

U2 - 10.1002/cmdc.201700755

DO - 10.1002/cmdc.201700755

M3 - Journal article

C2 - 29231283

SN - 1860-7179

VL - 13

SP - 236

EP - 240

JO - ChemMedChem

JF - ChemMedChem

IS - 3

ER -

Potent Inhibitors against Newcastle Disease Virus Hemagglutinin-Neuraminidase

Abstract

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