Influenza Virus Neuraminidase: Structure and Function

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Abstract


The structure of the influenza virus neuraminidases, the spatial organization of their active site, the mechanism of carbohydrate chains desialylation by neuraminidase, and its role in the influenza virus function at different stages of the viral infectious cycle are considered in this review. Data on the neuraminidase substrate specificity and different approaches in studying the activity of this enzyme are summarized. In addition, data on neuraminidase inhibitors (as antivirals) are provided, along with considerations on the mechanisms of resistance of modern influenza viruses to those antivirals.

The influenza virus is an enveloped (-)RN A containing a virus with a segmented genome, and its genetic material is coded by eight RN A-segments. All RN A segments are packed in a nucleocapsid protein, and a complex of polymerase proteins is attached to each of the genomic segments. Those RN A-protein complexes are packed in a lipoprotein envelope lined from the inside with a matrix protein, with haemagglutinin, neuraminidase, and M2 proteins exposed on the outer surface of the viral particle. Neuraminidase is an exosialidase (EC 3.2.1.18) which cleaves -ketosidic linkage between the sialic (N-acetylneuraminic) acid and an adjacent sugar residue [1]. The amino acid sequence of NA is coded by the 6th RN A segment. Nine subtypes of NA are described for influenza A, whereas only one NA subtype was revealed for the influenza viruses B and C [2]. Nine subtypes of influenza A NA are divided into two phylogenic groups. The first group consists of the neuraminidases of N1, N4, N5 and N8 subtypes, and the second one consists of N2, N3, N6 N7 and N9 subtypes [3]. The enzyme of the influenza C virus does not belong to the neuraminidase group. It promotes the O-deacetylation of the N-acetyl-9-O-acetylneuraminic acid, i.e. it belongs to the esterase family and will not be considered in this review.

Y A Shtyrya

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS

L V Mochalova

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS

N V Bovin

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS

Email: professorbovin@yandex.ru

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