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. Epub 2023 Feb 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Chlorocebus aethiops
  • HN Protein / chemistry
  • HN Protein / genetics
  • Hemagglutinins
  • Humans
  • N-Acetylneuraminic Acid* / pharmacology
  • Neuraminidase
  • Newcastle disease virus
  • Paramyxoviridae Infections*
  • Vero Cells

Substances

  • N-Acetylneuraminic Acid
  • Antiviral Agents
  • Neuraminidase
  • Hemagglutinins
  • HN Protein