2. Academic Validation
  3. Design, Synthesis, and Antiviral Evaluation of Sialic Acid Derivatives as Inhibitors of Newcastle Disease Virus Hemagglutinin-Neuraminidase: A Translational Study on Human Parainfluenza Viruses

Design, Synthesis, and Antiviral Evaluation of Sialic Acid Derivatives as Inhibitors of Newcastle Disease Virus Hemagglutinin-Neuraminidase: A Translational Study on Human Parainfluenza Viruses

  • ACS Infect Dis. 2023 Mar 10;9(3):617-630. doi: 10.1021/acsinfecdis.2c00576.
Paola Rota 1 2,  Paolo La Rocca 2 3,  Francesco Bonfante 4,  Matteo Pagliari 4,  Marco Piccoli 2 5,  Federica Cirillo 2 5,  Andrea Ghiroldi 2 5,  Valentina Franco 6 7,  Carlo Pappone 2 8 9,  Pietro Allevi 1,  Luigi Anastasia 2 5 9
Affiliations

Affiliations

  • 1 Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
  • 2 Institute for Molecular and Translational Cardiology (IMTC), San Donato Milanese, 20097 Milan, Italy.
  • 3 Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy.
  • 4 Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, 35020 Legnaro, Italy.
  • 5 Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy.
  • 6 Division of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
  • 7 IRCCS, Mondino Foundation, 27100 Pavia, Italy.
  • 8 Arrhythmology Department, IRCCS Policlinico San Donato, Piazza Malan 2, San Donato Milanese, 20097 Milan, Italy.
  • 9 Faculty of Medicine, University of Vita-Salute San Raffaele, 20132 Milan, Italy.
PMID: 36848501 DOI: 10.1021/acsinfecdis.2c00576
Abstract

Global infections with viruses belonging to the Paramyxoviridae, such as Newcastle disease virus (NDV) or human parainfluenza viruses (hPIVs), pose a serious threat to animal and human health. NDV-HN and hPIVs-HN (HN Hemagglutinin-Neuraminidase) share a high degree of similarity in catalytic site structures; therefore, the development of an efficient experimental NDV host model (chicken) may be informative for evaluating the efficacy of hPIVs-HN inhibitors. As part of the broad research in pursuit of this goal and as an extension of our published work on Antiviral drug development, we report here the biological results obtained with some newly synthesized C4- and C5-substituted 2,3-unsaturated sialic acid derivatives against NDV. All developed compounds showed high neuraminidase inhibitory activity (IC50 0.03-13 μM). Four molecules (9, 10, 23, 24) confirmed their high in vitro inhibitory activity, which caused a significant reduction of NDV Infection in Vero cells, accompanied by very low toxicity.

Keywords

Newcastle disease virus; antiviral inhibitor; hemagglutinin-neuraminidase; human parainfluenza viruses; sialic acid; viral infection.

Figures
Products