Forgione Rosa Ester, Di Carluccio Cristina, Milanesi Francesco, Kubota Marie, Fabregat Nieto Ferran, Molinaro Antonio, Hashiguchi Takao, Francesconi Oscar, Marchetti Roberta, Silipo Alba
Department of Chemical Sciences, Complesso Universitario Monte Sant'Angelo, University of Naples Federico II, Naples, Italy.
Department of Chemistry "Ugo Schiff" and INSTM, University of Florence Polo Scientifico e Tecnologico, Florence, Italy.
Front Chem. 2021 Oct 27;9:711346. doi: 10.3389/fchem.2021.711346. eCollection 2021.
The inhibition of surface viral glycoproteins offers great potential to hamper the attachment of viruses to the host cells surface and the spreading of viral infection. Mumps virus (MuV) is the etiological agent of the mumps infectious disease and causes a wide spectrum of mild to severe symptoms due to the inflammation of the salivary glands. Here we focus our attention on the hemagglutinin-neuraminidase (HN) isolated from MuV SBL-1 strain. We describe the molecular features of host sialoglycans recognition by HN protein by means of NMR, fluorescence assays and computational studies. Furthermore, we also describe the synthesis of a N-acetylneuraminic acid-derived thiotrisaccharide targeting the viral protein, and the corresponding 3D-complex. Our results provide the basis to improve the design and synthesis of potent viral hemagglutinin-neuraminidase inhibitors.
抑制病毒表面糖蛋白具有巨大潜力，可阻碍病毒附着于宿主细胞表面并阻止病毒感染的传播。腮腺炎病毒（MuV）是腮腺炎传染病的病原体，由于唾液腺炎症可导致一系列从轻度到重度的症状。在此，我们将注意力集中于从MuV SBL-1株分离出的血凝素神经氨酸酶（HN）。我们通过核磁共振、荧光测定和计算研究描述了HN蛋白识别宿主唾液酸聚糖的分子特征。此外，我们还描述了一种靶向该病毒蛋白的N-乙酰神经氨酸衍生硫代三糖的合成及其相应的三维复合物。我们的结果为改进强效病毒血凝素神经氨酸酶抑制剂的设计与合成提供了依据。
