Exploring human parainfluenza virus type-1 hemagglutinin-neuraminidase as a target for inhibitor discovery.

Abstract

Human parainfluenza virus type 1 is the major cause of croup in infants and young children. There is currently neither vaccine nor clinically effective treatment for parainfluenza virus infection. Hemagglutinin-neuraminidase glycoprotein is a key protein in viral infection, and its inhibition has been a target for 2-deoxy-2,3-didehydro-d-N-acetylneuraminic acid (Neu5Ac2en)-based inhibitor development. In this study, we explore the effect of C-5 modifications on the potency of Neu5Ac2en derivatives that target the human parainfluenza type-1 hemagglutinin-neuraminidase protein. Our study demonstrates that the replacement of the Neu5Ac2en C-5 acetamido moiety with more hydrophobic alkane-based moieties improves the inhibitory potency for both hemagglutinin-neuraminidase functions. These findings shed light on the importance of C-5 substitution on Neu5Ac2en in the design of novel sialic acid-based inhibitors that target human parainfluenza type-1 hemagglutinin-neuraminidase.

• Authors: Ibrahim M El-Deeb, Patrice Guillon, Moritz Winger, Tanguy Eveno, Thomas Haselhorst, Jeffrey C Dyason, Mark von Itzstein
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 57 Issue 18 Pg. 7613-23 (Sep 25 2014) ISSN: 1520-4804 [Electronic] United States
• PMID: 25198831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Antiviral Agents
• HN Protein

Topics

• Amides (chemistry, pharmacology)
• Animals
• Antiviral Agents (chemistry, pharmacology)
• Cell Line
• Drug Evaluation, Preclinical
• HN Protein (chemistry, metabolism)
• Inhibitory Concentration 50
• Molecular Dynamics Simulation
• Parainfluenza Virus 1, Human (drug effects)
• Protein Conformation