title: 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.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus , Gold Coast, Queensland 4222, Australia.
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Deeb
authors.forename: Patrice
authors.initials: P
authors.lastname: Guillon
authors.forename: Moritz
authors.initials: M
authors.lastname: Winger
authors.forename: Tanguy
authors.initials: T
authors.lastname: Eveno
authors.forename: Thomas
authors.initials: T
authors.lastname: Haselhorst
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Dyason
authors.forename: Mark
authors.initials: M
authors.lastname: von Itzstein
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D015707:HN Protein / Q000737:chemistry / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D056004:Molecular Dynamics Simulation; D010222:Parainfluenza Virus 1, Human / Q000187:drug effects*; D011487:Protein Conformation
chemical_list: D000577:Amides; D000998:Antiviral Agents; D015707:HN Protein