ИСТИНА

Influenza virus is a widespread pathogen that causes epidemics of flu. The World Health Organization mentioned influenza pandemic as one of ten threats to global health in 2019. The hemagglutinin (HA) is the most presented protein on the surface of influenza virus particle. HA is responsible for recognition and attachment to the mammalian cell, which makes HA a potential target for antiviral agents. In this study the structural and functional characteristics of some aptamers to HA are given. The non-canonical DNA structures of RHA0385 and BV42 aptamers to HA were firstly studied with nuclear magnetic resonance (NMR) method and spectroscopy of circular dichroism (CD). Aptamers’ affinity to recombinant HAs and the influenza viruses of different strains was determined by different methods: surface plasmon resonance (SPR), biolayer interferometry (BLI) and enzyme-linked aptamer assay (ELAA). One of these aptamers, RHA0385, was demonstrated to have broad strain-specificity. After the structural and functional studies of original aptamer, several derivatives were generated and characterized. A set of X-ray structures of aptamer–protein complexes was analyzed. It was found that the complexes of aptamers with modified nucleotides have more pronounced structure–affinity relationship (SAR) compared to complexes with unmodified ones. The affinity increases with the increase in interface area between aptamer and protein in complex. The overall theoretical analysis and experimental data yielded the paradigm that aptamer RHA0385 has a rigid 3D DNA scaffold and a flexible loop which is responsible for interactions with HA. Alteration of the loop affects both structural stability and function of the aptamer. This work was supported by the Russian Scientific Foundation [grant number 18-74-10019].