A dramatic increase of influenza activity in Russia since week 3 of 2016 significantly differs from previous seasons in terms of the incidence of influenza and acute respiratory infection (ARI) and in number of lethal cases. We performed antigenic analysis of 108 and whole‐genome sequencing of 77 influenza A(H1N1)pdm09 viruses from Moscow and Saint Petersburg. Most of the viruses were antigenically related to the vaccine strain. Whole‐genome analysis revealed a composition of specific mutations in the internal genes (D2E and M83I in NEP, E125D in NS1, M105T in NP, Q208K in M1, and N204S in PA‐X) that probably emerged before the beginning of 2015/2016 epidemic season.

The COVID-19 pandemic had a profound impact on influenza activity worldwide. However, as the pandemic progressed, influenza activity resumed. Here, we describe the influenza epidemic of high intensity of the 2022–2023 season. The epidemic had an early start and peaked in week 51.2022. The extremely high intensity of the epidemic may have been due to a significant decrease in herd immunity. The results of PCR-testing of 220,067 clinical samples revealed that the influenza A(H1N1)pdm09 virus dominated, causing 56.4% of positive cases, while A(H3N2) influenza subtype accounted for only 0.6%, and influenza B of Victoria lineage—for 34.3%. The influenza vaccine was found to be highly effective, with an estimated effectiveness of 92.7% in preventing admission with laboratory-confirmed influenza severe acute respiratory illness (SARI) cases and 54.7% in preventing influenza-like illness/acute respiratory illness (ILI/ARI) cases due to antigenic matching of circulated viruses with influenza vaccine strains for the season. Full genome next-generation sequencing of 1723 influenza A(H1N1)pdm09 viruses showed that all of them fell within clade 6B.1A.5.a2; nine of them possessed H275Y substitution in the NA gene, a genetic marker of oseltamivir resistance. Influenza A(H3N2) viruses belonged to subclade 3C.2a1b.2a.2 with the genetic group 2b being dominant. All 433 influenza B viruses belonged to subclade V1A.3a.2 encoding HA1 substitutions A127T, P144L, and K203R, which could be further divided into two subgroups. None of the influenza A(H3N2) and B viruses sequenced had markers of resistance to NA inhibitors. Thus, despite the continuing circulation of Omicron descendant lineages, influenza activity has resumed in full force, raising concerns about the intensity of fore coming seasonal epidemics.

Glycyrrhizic acid (GA) conjugates with methyl and ethyl esters of D-amino acids (D-Trp, D-Phe, D-Tyr, D-Val, D-Leu) have been synthesized by the activated esters method using mixtures of N-hydroxybenzotriazole or N-hydroxysuccinimide with N,N′-dicyclohexylcarbodiimide. GA conjugate with D-Trp ethyl ester exhibited antiviral activity against influenza viruses A/H3N2, A/H1N1/pdm09, A/H5N1, B (SI > 10–29), and HRSV (SI > 25). GA conjugate with D-Trp methyl ester inhibited influenza virus A/H1N1/pdm09 (SI > 30).

There are presented data of Federal Influenza Center of Russia on morbidity of influenza, intensity, duration, geographical spread of epidemic, recorded lethal outcomes with laboratory-confirmed diagnosis "influenza" in the season of 2014-2015. The epidemic in this season was more intensive in character in comparison to the previous season according to most of the indices. Main etiologic agents were influenza B - 50,6 % of isolated strains, the portion of influenza A(H3N2) viruses accounted for 45 % of isolates and pandemic influenza 2009 virus was revealed only in 4,35 % of studied clinical materials. Incomplete compliance of influenza vaccine for the component A (H3N2), observed in the world in 2015, and especially the further evolution of this group of viruses in the current season demonstrate the importance of the widest possible coverage by epidemiological studies, isolation of the virus in different periods of the epidemic season in different geographical regions and etiological analysis of them with the use of modern methods for the increase of the efficacy of vaccination

Relevance. The improvement of the surveillance of evolution of influenza viruses and the refinement of the capacity of prognostics of their evolutionary tendencies would lead to the better understanding and control on influenza epidemics. Aim. Establish the etiological nature of influenza epidemics in 2020–2023 in Russia and the antigenic properties of influenza viruses of the types A and B which circulated on its territory in 2020–2023. Methods. Isolation of influenza viruses from PCR+-clinical materials (nazo-pharingeal swabs and post-mortem tissue samples) in the cell lines MDCK and MDCK-Siat1; antigenic analysis by means of the reaction of hemagglutination-inhibition (HI) and micro-neutralization (MN) with the cell-ELISA detection using the post-infectious ferret antisera and rat polyclonal antisera; antigenic cartography. Results and discussion. The season 2020–2021 – the 1st season of pandemic of COVID-19, was characterized by quasi-total disappearance of influenza viruses from human population on the territory of REussia, probably as a consequence of stringent sanitary-hygienic measures worldwide due to COVID-19 pandemic. In the next epidemic season we could observe the domination of influenza viruses A(H3N2) during all season with the slight growth of the proportion of influenza B in the second part of the season. We could not isolate influenza viruses A(H1N1)pdm09 in that season due to their low epidemic activity, and the majority of isolated strains were А(H3N2) viruses – 94,4% of the total number of isolates. Influenza Вvic consisted 28 % of all number of isolates. The season 2022-23, opposite to the previous one, was characterized by the domination of influenza viruses of the sub-type А(H1N1)pdm09 what made it different from the epidemic in Europe and North America, where the A(H3N2) were prevalent, particularly in the first half of the epidemic season. Later on, the situation in Europe has changed and, as in Russia, influenza B actively introduced in circulation. The proportion of isolation of influenza viruses A(H1N1) pdm09 in Russia was 69,2 %, of influenza A(H3N2) – 3,5 %, of influenza Вvic – 27,3 %. Activation of A(H1N1)pdm09 viruses was probably a result of emergence of drift-variants of this sub-type during the epidemics what was supported by the data of antigenic and genetic analyses. Thus in 2020 the first isolates of a genetic clade 6В.1А5а were discovered. They possessed the key substitution N156K in the antigenic site Sb of НА1. The results of genetic analysis have shown that among the A(H1N1)pdm09 viruses of the last season which belonged to the clade 6В.1А.5а.2а, a group of viruses carrying the substitutions P137S, K142R, D260E, T277A in HA1 could be found, which are also present in the new vaccine strain А/Victoria/4897/2022 (genetic sub-group 6В.1А.5а.2а.1). This virus was recommended for the next season 2023-2024 for the Northern Hemisphere. Concerning the antigenic properties, the viruses having such substitutions practically did not differ from the majority of strains A(H1N1)pdm09 in circulation during the last season. So influenza A(H1N1)pdm09 viruses, that circulated in Russia in 2022-2023 represented the antigenic cluster of A/Victoria/2570/2019-like strains. They were also similar to the strain A/Victoria/4897/2022, which was recommended by the WHO experts for the composition of vaccines for the season 2023–2024. The majority of viruses A(H3N2) have preserved the ability to agglutinate erythrocytes of mammals in the presence of 20 nM oseltamivir carboxylate, that is why we applied for their characterization the HI-test. The strains under study were very close to the strain A/Darwin/09/21, recommended by the WHO as the vaccine strain for the season 2022-2023. They belonged to the most wide-spread in the World genetic group 3С.2а1b.2a.2. All studied influenza B viruses belonged to the Victoria lineage and were B/Austria/1359417/2021-like. According to the phylogenetic analysis, all modern Victoria strains clustered into the sub-clade V1A.3a.2, coding the substitutions A127T, P144L и K203R in HA1. Inside this clade one can determine two genetic sub-groups: the 1st include viruses with the substitution in the HA1-protein D197E and the second – a group of viruses with the substitutions E128K, A154E, S208P in НА1. Strains of the Yamagata lineage were not registered on the territory of Russia since 2021, so the problem of their antigenic drift and possible return into circulation stays opened. The very low level of circulation of influenza viruses in 2020-2021 complicated the prognostics and selection of vaccine strains. According the results of HI- and MN-tests we could conclude that in 2021-2022 there was a partial consistency between the vaccine strain A/Cambodia/е0826360/20 (H3N2) and the strains in circulation which were more like to the reference strain A/ Darwin/9/21. We could also observe a mismatch of influenza viruses B in circulation and the vaccine variant B/Washington/02/19. As a result of the propagation of drift variants, the substitution of vaccine strains was made for the Northern Hemisphere for 2022/23. For the H3 component the strain A/Darwin/09/21 was introduced, and for Bvic component –B/Austria/1359417/21. Conclusion. In the period under consideration the relative homogeneity of population was observed inside each type and sub-type of influenza viruses and their fitness to the actual vaccine strains. However the selection of the strains – candidates for seasonal vaccines still remains a serious problem. Thus, in the season 2019-2020 one could observe a mismatch of the vaccine strain and the viruses in circulation in Russia for the component A(H3N2) and partial mismatch for the component B Victoria. In the season 2021-22 was evident a mismatch for Bvic and partial conformity for the component A(H3N2) and only in the last season 2022-23 we could confirm a complete fitness of the vaccine composition and the viruses in the circulation. The timely submission of data and samples to the WHO CCs promotes decision-making on the selection of strains and their introduction into influenza vaccines for the future epidemic season. The sustainability of the epidemiologic surveillance and the refinement of the methods of analysis of antigenic, genetic and other biological properties of circulating viruses would enhance the level of preparedness of healthcare system to the yearly influenza epidemics in the country.

Introduction. Human metapneumovirus (hMPV) holds significant epidemiological importance, being a dominant cause of lower respiratory tract infections in children under two years of age and individuals over 65. Multiple infections with hMPV throughout a person’s life are possible due to the antigenic and genetic variability of the virus. However, the genetic variability of hMPV circulating in Russia remains unexplored. Aim of the study. The aim of this study was to test a protocol for whole-genome sequencing of hMPV to assess the genetic diversity of metapneumoviruses circulating in certain regions of Russia. Materials and methods. Nasopharyngeal swabs were collected from patients of different ages with acute respiratory viral infections (ARVI) tested positive for hMPV using polymerase chain reaction (PCR). From some of the samples, viral isolates were obtained in cell culture. Whole-genome sequencing was performed on both swabs and isolates using the MiSeq Illumina platform, followed by phylogenetic analysis. Results. For the first time in Russia, whole-genome sequencing of 44 hMPV strains circulating from 2017 to 2024 was conducted. Their genetic group affiliation was described, with the A2b2 clade shown to dominate. It was confirmed that the greatest variability among genes encoding viral surface proteins was observed in the G gene, while changes in the F gene were minimal during the studied period. Conclusion. The study provides insights into the genetic diversity of hMPV strains circulating in various regions of the Russian Federation. Understanding the genetic variability of hMPV is crucial for comprehending viral evolution, transmission dynamics, and mechanisms of immune evasion, which influence the development of vaccines and antiviral drugs.