The Cytotoxicity indices (IC50) of Keggin’s phosphorus-molybdenum heteropoly acids (HPCAs) and their sodium and potassium salts on dog kidney cells (MDSC) were determined. The antiviral activity of these compounds against topical strains of influenza A (H3N2 and H1N1) was revealed. The dependence of the biological properties of polyoxometalates (POMs) on the elemental composition of their molecules has been confirmed. It has been shown that when some of the molybdenum atoms are replaced by vanadium atoms, HPCA and their salts acquire higher cytotoxicities, which increase monotonically as the number of substitutions increases. For the first time, the dependence of the biological activity of HPCA and their salts on the mass of cations has been established and interpreted. In vivo (on white outbred mice) the values of semi-lethal doses (DL50) of these compounds were established. For aqueous solutions of sodium and potassium salts of GPCA in a wide range of concentrations (from 0.05 μM to 15 μM), the values of the toxicity index (It) were determined on the model of motile cells. It has been established that GPCA and their salts are classified as moderately dangerous toxic substances and have selective antiviral activity, which at low concentrations (less than 15 μM) for influenza A strains is manifested mainly by a decrease in hemagglutination activity (HA).

The antiviral activity of Keggin heteropolyacids (HPAs) against the human influenza A/California/07/09 (H1N1) pdm09 virus is studied in MDCK cell culture. Transmission electron microscopy reveals new features of the destruction of viral particles by HPAs. A proton-anion model that considers the main biochemical processes leading to the destruction of enveloped viruses: the depletion of membrane cholesterol by HPA anions, acidification of the M1 matrix protein by protons of the medium, and anion lysis of lipid membranes, is proposed. The Arrhenius dependences of the biological properties of HPAs on temperature are predicted. The general mechanism for the formation of high biological activity HPAs is described, which is underlined by the anion depletion of cholesterol in bilipid membranes, a new effect in the biochemistry of polyoxometalates.

The results of an electron microscopic study of the effect of heteropoly acids (HPAs) with a Keggin structure on particles of influenza A/Aichi/1/68 (H3N2) and A/California/07/09 (H1N1) pdm09 viruses are presented. It is shown that the action of HPAs on viral particles leads to a complete (or partial) removal of transmembrane glycoproteins and the destruction of matrix protein M1, which manifests itself in the deformations and destruction of viral membranes. Using the A/California/07/09 (H1N1) pdm09 viruses as an example, it is shown that the efficiency of the destruction of the viral envelope by HPAs depends on the medium in which the viruses are cultured. The mechanism of destruction is proposed, which involves the extraction of cholesterol, etching of phospholipids, and the formation of pores in the lipid membrane as a result of the action of heteropolyanions. It is assumed that the penetration of protons through the formed pores can lead to the destruction of the matrix protein M1.

Considering the wide spread of known and new pathogens of acute respiratory viral infections (ARVI), it is important to search for drugs that have a wide spectrum of antiviral activity and additionally the ability to act pathogenetically Equally important is the confirmation of therapeutic activity in drugs known for their effectiveness and safety In order to monitor the susceptibility of ARVI pathogens to the antiviral drug Influcid, a series of in vitro studies was performed Materials and methods: classical virological controlled studies were performed using current strains of human influenza virus (A/Moscow/225/2019 (H1N1)pdm09 and B/Moscow/17/2019) and MDCK cell culture Antiviral, cytoprotective (against viruses, antiviral and antipyretic drugs) properties of the Inflicid were evaluated by changing the logarithm of the tissue cytopathic infecting dose, which causes 50% of cells to be damaged (lgTCID50), as well as by changing the optical density when using tetrazolium dyes Results and discussion: Influcid dose-dependently suppressed the reproduction of epidemic strains A/Moscow/225/2019(H1N1)pdm09 and B/Moscow/17/2019 by 50% at concentrations of 0, 34 and 0, 69-0, 86% vol , respectively Also, the Influcid reduced the reproduction of human influenza virus strains: A/New Caledonia/20/99(H1N1), A/Victoria/35/72, Wisconsin/67/05(H3N2) and B/Malaysia/2506/04, reducing the titers by 0, 5-2, 5 lgTCID50 and Dengue virus DENV-2/RUS/TH-Novosibirsk02/2012 Influcid exerted a cytoprotective effect on cells infected with A/IIV-Moscow/01/2009 (H1N1)pdm09, increasing the proportion of surviving cells by 4-52, 0% For cells infected with the pandemic strain A/California/07/09(H1N1)pdm09, there was a significant decrease in the cytopathic effect of the virus up to full protection with the «preventive» scheme of the drug application In addition, the Influcid protected cells from the action of herpes viruses types I and II, type III adenovirus, parainfluenza virus, seasonal coronavirus and respiratory syncytial virus, toxic doses of umifenovir and rimantadine, and did not increase the cytotoxicity of acetaminophen and ibuprofen Conclusion: having a combination of confirmed antiviral activity against current epidemic virus strains, cytoprotective action, the ability to exert a pathogenetic (immunomodulatory and anti-inflammatory) effect, as well as a favorable safety profile, Influcid may be a relevant and promising drug in the arsenal of medical practitioners

The strong dependence of cytotoxicity of Keggin heteropoly acids [XM12O40]n–, X = Si or P, M = Mo and W, n = 3 or 4 on chemical composition is demonstrated using the example of human embryo fibroblast cells based on the results of diagnostics using impedance monitoring, scanning electron microscopy, and measurements of visible cell sizes. The explanation of this dependence based on the role of hydrolytic stability of multiply charged anions in the development of cytotoxicity of these compounds is suggested. The results make it possible to suggest a new mechanism for the development of selectivity of polyoxometalate cytotoxicity relative to the studied cells. The differentiated cytotoxic activity of polyoxometalates relative to oncogenic cells is predicted.

На примере клеток фибробластов эмбриона человека по результатам диагностики с использованием методов импедансного мониторинга, растровой электронной микроскопии, а также измерений видимых размеров клеток продемонстрирована сильная зависимость цитотоксичности гетерополикислот Кеггина [XM 12 O 40 ] n- , Х = Si и Р, М = Мо и W, n = 3 или 4, от химического состава. Предложено объяснение выявленной зависимости, основанное на роли гидролитической стабильности многозарядных анионов в формировании цитотоксичности этих соединений. Полученные результаты позволяют предположить новый механизм формирования селективности цитотоксичности полиоксометаллатов в отношении исследованных клеток. Прогнозируется дифференцированная цитотоксическая активность полиоксометаллатов в отношении онкогенных клеток.

The results of the ultrastructural study of the epithelium of the patient cervix infected by the human papillomavirus (HPV) types 16 and 18 before and after treatment by contrasting thermo-laser therapy (CTLT) are presented. It was shown in this work that 1.5 and 6 months after treatment HPV DNA was not detected in the biopsy and the smear of the cervix using the polymerase chain reaction (PCR). In the ultrathin sections, the structure of the epithelial cells from the biopsy after treatment corresponded to norm. There was effective elimination of HPV types 16 and 18 as Induces by CTLT method.

The results of the virological identification of the Chikungunya fever case in Moscow (September, 2013) in an Indonesian visitor are presented. The clinic, electron microscopy, and molecular genetic data are discussed. The Ghikungunya virus (CHIKV) strain CHIKVILEIV-Moscow/1/2013 belonging to the Asian genotype (ID GenBank KF872195) was deposited into the Russian State Collection of viruses (GKV 1239; 18.11.2013).

The results of the ultrastructural study of the epithelium of the patient cervix infected by the human papillomavirus (HPV) types 16 and 18 before and after treatment by contrasting thermo-laser therapy (CTLT) are presented. It was shown in this work that 1.5 and 6 months after treatment HPV DNA was not detected in the biopsy and the smear of the cervix using the polymerase chain reaction (PCR). In the ultrathin sections, the structure of the epithelial cells from the biopsy after treatment corresponded to norm. There was effective elimination of HPV types 16 and 18 as induces by CTLT method.

Virus particles are typically consisted of several hundreds to thousands of protein molecules, which self-assembled to form hollow scaffold containing the viral nucleic acid (RNA or DNA). They ranged in sizes from ~ 10 nm to over a micron and can be found in variety of distinctive shapes (icosahedrons, spheres, rodes). As an emerging and important nanocarrier platform, viruses and virus-like particles (VLP) offer the great advantages of morphological uniformity, biocompatibility and polyfunctionality. In recent years, viruses and VLPs are tailorable at the genetic level for application as reagents, catalysts and scaffolds for chemical reactions, effective vectors for targeted drug delivery and suitable platform for candidate vaccine constructions. This review describes approaches to use viruses in different spheres of nanotechnology and nanomedicine for the next generation therapeutics and imaging devices, as nanocomposites with chemical compounds and metals for new diagnostic methods and even in electronics. Several examples in nanobiomedicine researches at D.I. Ivanovsky Institute of Virology (new diagnostic biochips for influenza A subtypes differentiation, latex-agglutination method for HCV antibodies detection, atomic force microscopy in clinics, TMV recombinants expressing influenza HA antigenic epitopes, polyanylin and nanodiamonds as effective biosorbents) are mentioned as promissive for future development.

Different cell tissue cultures and commercial fetal calf sera (FTS) used in biological and virological research were screened for the bovine viral diarrhea virus (BVDV, Pestivirus genus, Flaviviridae family) and mycoplasma contamination. BVDV was detected using RT-PCR and Indirect immunofluorescence (with monoclonal antibodies) methods in 33% cases of the studied cell lines and in > 60% cases of FCS. BVDV was shown to present and reproduce in high spectra of human cell lines, as well as in monkey, pig, rabbit, goat, dog, and cat cells at high levels (up to 100-1000 genome-equivalent copies per cell) and reached up to 10(3)-10(7) genome-equivalent copies per serum ml. The molecular mechanisms of the long virus persistence without definite signs of destruction should be studied.