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Effects of Oligoribonucleotides-D-Mannitol Complexes on the Hemagglutinin-Glycan Interactions
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1  Institute of Molecular Biology and Genetics National Academy Science of Ukraine, Kyiv, Ukraine

Published: 14 November 2016 by MDPI in 2nd International Electronic Conference on Medicinal Chemistry session ECMC-2

The influenza virus surface glycoprotein hemagglutinin (HA) is responsible for viral attachment to sialic acid-containing host cell receptors and it facilitates the initial stage of viral infection. Natural and synthetic oligoribonucleotides (ORNs) have a wide range of biological activities and can be used in antiviral treatments since they play a key role in antiviral activity and can change a conformation of some proteins. In our previous study it was shown that complexes of ORNs with D-mannitol (ORNs-D-mannitol) have higher antiviral activity against influenza A viruses than ORNs. However, the mechanism of ORNs-D-mannitol antiviral activity is still not clear. So the effects of the ORNs-D-mannitol on HA-glycan interactions were studied. Also interactions between the ORNs-D-mannitol and HA were determined.

It was shown that ORNs-D-mannitol have ability to interfere with HA-glycan interactions. A decrease of HA activity of influenza A (A/FM/1/47(H1N1)) virus by a factor 4 was observed after incubation of virus with ORNs-D-mannitol in comparison to the virus control.

Reduction of the fluorescence intensity of HA of flu virus in the presence of the ORNs-D-mannitol was observed. This effect may indicate that interactions between  HA and ORNs-D-mannitol are responsible for conformation changes of HA. For further verification of this assumption we used fluorescence data to calculate dissociation constants that appeared to be relatively weak (micromolar) in our case (kd = 4.91μM).

 Our research demonstrates that ORNs-D-mannitol complexes bind to HA of flu virus and in this manner inhibit HA-glycan interactions. It allows us to assume that changes of HA conformations could explain the antiviral activity of those ORNs-D-mannitol complexes.