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

Ibrahim M El-Deeb, Patrice Guillon, Moritz Winger, Tanguy Eveno, Thomas Haselhorst, Jeffrey C Dyason, Mark von Itzstein

Journal of medicinal chemistry 2014 Sep 25

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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.

Citation

Ibrahim M El-Deeb, Patrice Guillon, Moritz Winger, Tanguy Eveno, Thomas Haselhorst, Jeffrey C Dyason, Mark von Itzstein. Exploring human parainfluenza virus type-1 hemagglutinin-neuraminidase as a target for inhibitor discovery. Journal of medicinal chemistry. 2014 Sep 25;57(18):7613-23