Interplay of Modified Sialic Acid Inhibitors and the Human Parainfluenza Virus 1 Hemagglutinin-Neuraminidase Active Site
Articolo
Data di Pubblicazione:
2023
Citazione:
Interplay of Modified Sialic Acid Inhibitors and the Human Parainfluenza Virus 1 Hemagglutinin-Neuraminidase Active Site / P. Rota, P. La Rocca, F. Bonfante, M. Pagliari, F. Cirillo, M. Piccoli, A. Ghiroldi, V. Franco, C. Pappone, P. Allevi, L. Anastasia. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 14:10(2023 Oct 12), pp. 1383-1388. [10.1021/acsmedchemlett.3c00291]
Abstract:
In the search for effective antivirals against Paramyxoviridae, the dynamics of human parainfluenza virus type 1 hemagglutinin-neuraminidase (hPIV1-HN) inhibition offers a promising perspective. This study focuses on the potential of C5- and C4-modified 2,3-unsaturated sialic acid (DANA) inhibitors and highlights their interaction with the hPIV1-HN enzyme. We show that a strategic substitution, replacing the C5 isopropyl group in BCX 2798 with a trifluoroacetyl function, increases inhibitory potency 3- to 4-fold. At the same time, we explore the special properties of the catalytic site of hPIV1-HN, which harbors only small substituents and favors a C4 sulfonyl-amido function over a carbonyl function, in contrast to the C4 pocket of Newcastle disease virus hemagglutinin-neuraminidase (NDV-HN). Based on these findings, we present a newly identified potent inhibitor that has the preferred C5 trifluoro-acetamido and C4 trifluoro-sulfonyl-amide groups. The results of this study pave the way for a deeper understanding of the C4 and C5 binding pockets of hPIV1-HN and promote the development of new, more selective inhibitors.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
human parainfluenza virus 1; sialic acid; antiviralinhibitor; hemagglutinin-neuraminidase; viral infection
Elenco autori:
P. Rota, P. La Rocca, F. Bonfante, M. Pagliari, F. Cirillo, M. Piccoli, A. Ghiroldi, V. Franco, C. Pappone, P. Allevi, L. Anastasia
Link alla scheda completa: