Characterization of Natural and Synthetic Sialoglycans Targeting the Hemagglutinin-Neuraminidase of Mumps Virus.

Antonio Molinaro,Takao Hashiguchi,Ferran Fabregat Nieto,Marie Kubota,Oscar Francesconi,Cristina Di Carluccio,Roberta Marchetti,Rosa Ester Forgione,Francesco Milanesi,Alba Silipo

doi:10.3389/fchem.2021.711346

Abstract

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.

Highlights

Mumps is an infectious disease with a high morbidity in non-immunized children, caused by a respiratory-droplets transmitted virus, known as mumps virus
Receptor motifs that can be recognized by Mumps virus (MuV)-HN protein from SBL-1 strain have been recently identified by glycan array screening (Kubota et al, 2019) as specific host-cell sialoglycans which terminate with neuraminic acid (Neu5Ac) moiety
Hemagglutinin-Neuraminidase activity is essential for the infection and propagation of viruses belonging to the Paramyxoviridae family, including parainfluenza, the Newcastle disease and mumps viruses

Summary

Introduction

Mumps is an infectious disease with a high morbidity in non-immunized children, caused by a respiratory-droplets transmitted virus, known as mumps virus. It causes swollen salivary glands under the ears, referred to as parotitis; other symptoms include fever, headache, muscle aches and tiredness. In adults, mumps can cause orchitis, mastitis, pancreatitis, encephalitis and meningitis. Despite the advent of an effective vaccine, mumps virus continues to circulate throughout the world and the majority of mumps infections are subclinical in vaccinated individuals, severe complications still occur especially in underdeveloped countries. Different glycoproteins spikes protrude away from the viral surface, playing key roles in the different steps of the infection process as host receptor recognition, binding and cleavage. Among the 8 gene-encoded viral glycoproteins, exhibiting hemagglutinin, neuraminidase and cell fusion activity, hemagglutinin-neuraminidase (HN) has

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