Complexes of Oligoribonucleotides with D-Mannitol Inhibit Hemagglutinin-Glycan Interaction and Suppress Influenza A Virus H1N1 (A/FM/1/47) Infectivity In Vitro.

Nataliia Melnichuk,Zenoviy Tkachuk,Larisa Semernikova

doi:10.3390/ph10030071

Abstract

The influenza virus hemagglutinin (HA) mediates both receptor (glycan) binding and membrane fusion for cell entry and has been the basis for subtyping influenza viruses. The oligoribonucleotides-d-mannitol (ORNs-d-M) complexes possess an anti-influenza activity in vitro and in vivo. In the present studies, we have found that ORNs-d-M interferes with hemagglutinin (HA)–glycan interaction and suppress viral infection in host cells. HA–glycan interactions were evaluated to indirectly quantify the amount of influenza virus titer by an agglutination assay. Influenza virus infectivity was determined by TCID50 assay. The direct virucidal action of the complexes was evaluated by both cytopathic effects (CPE) reduction assay and cell MTT assay. We found that ORNs-d-M hinders interaction between HA and glycan. These complexes decreased the infectivity of influenza virus and had a direct virucidal action. ORNs-d-M reduces influenza virus infectivity, affecting the HA–glycan interaction in vitro. By suppressing the influenza viral infection, the ORNs-d-M can have direct virucidal action.

Highlights

Influenza virus belongs to the Orthomyxoviridae family and consists of four types: A, B, C, and D
The red blood cells (RBCs) agglutinated by the influenza virus were maintained in a suspended distribution and looked as a diffuse reddish solution
The RBCs agglutination by the influenza virus preincubated with the 2.5 mg/mL of ORNs and 3.5 mg/mL of ORNs-D-M was decreased compared with the influenza control, whereas agglutination of the RBCs by influenza virus preincubated with the 1.0 mg/mL of D-M and 0.35 and 0.035 mg/mL of ORNs-D-M remained unchanged

Summary

Introduction

Influenza virus belongs to the Orthomyxoviridae family and consists of four types: A, B, C, and D. Among these types, the influenza A viruses causes major infections in respiratory tract of humans and lower mammals, and in gastrointestinal tract of birds, making it responsible for numerous deaths and great economic losses every year. The influenza A viruses are classified into 16 HA (H1–H16) and 9 NA (N1–N9) sub-types of which H1–H3 have successfully adapted to humans [1,2]. Both HA and NA are important antigens that determine antigenic variation of the influenza viruses and host immunity. Variability in HA is primarily responsible for the continual evolution of new strains and subsequent influenza epidemics [3]

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