The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012–2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy)carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 μM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility − high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) − this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.

This paper presents a technology for formation of biocompatible material for bone defect regeneration based on carbon nanotubes and biopolymers. Studies of the structure of the formed samples indicate the presence of the necessary characteristics. Biocompatibility studies have shown the applicability of the developed material for the regeneration of large tissue defects.

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).

Studies of the morphological features and influence of photosensitized WS2, MoS2, and ZnS nanoparticles synthesized by laser ablation and fragmentation in liquid on human fibroblast cells are presented. Microscopy data showed that all types of nanoparticles were spherical in shape, except for WS2 nanoparticles, which were planar. Spherical nanoparticle sizes ranged from 20 to 90 nm, which meets the requirements for theranostics. Cytotoxicity studies demonstrated that MoS2 nanoparticles had high biocompatibility, while other nanoparticle types slowed cell growth, indicating future potential for use in the treatment of various diseases in living organisms.

Cell-free supernatant of Lactobacillus plantarum exhibit a strong antimicrobial effect against a number of pathogenic enterobacteria ( E. coli , Shigella flexneri , Salmonella typhimurium , Proteus mirabilis , and Campylobacter jejuni ). The degree of growth inhibition in broth culture reached a high level for all tested bacteria. The highest rates were noted for P. mirabilis (by 13 times) and the lowest for S. flexneri (by 5 times) and C. jejuni (by 4.5 times). Significant antiproliferative effect of the supernatant on cells of tumor-derived epithelial cell lines was shown. The highest degree of inhibition (by 22 times) was observed for HT-29 cells (colon carcinoma). Thus, inclusion of probiotics in traditional treatment schemes can increase the effectiveness of antibacterial and antitumor drug therapy.

Correlations between the immunomodulatory properties of heteropoly acids (HPAs) and the stiffness of target cells, which depend on the content of membrane cholesterol, are established. A molecular model of the cellular activation of immunoactive cytokine (CT) genes by heteropoly acids is constructed. The specific features of the immunomodulatory properties of HPAs in relation to healthy and cancer cells (HFFs, A549, and L41 lines) are discussed. A mechanism for the formation of increased antiviral activity of HPAs against (+)ssRNA viruses is proposed. We substantiate the possibility of the increased nonspecific antiviral activity of HPAs against pandemic strains of SARS-CoV-2, inactivation of which may involve HPA-activated cytokines.

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.

Carbon nanotubes (CNTs) are very promising for use in various areas of human activity, including medicine, but they can have a negative effect on the body, in particular on the nervous system. CNTs in large doses in animal experiments often cause anxiety and depressive disorders. The effect of low doses of CNTs on the behavior of animals has been little studied. In the present work, we studied behavioral parameters in tests for anxiety in rats, which were intranasally injected daily for 4 days with a suspension of single-walled carbon nanotubes (SWCNTs) in small doses, 5.2 µg/kg or 52 µg/kg. It turned out that both doses of SWCNTs unidirectionally changed the following indicators of behavior in rats: in the open field test exploratory activity (rears) decreased; in the light–dark box test the latency of entering to the dark box and peeping out of the dark box and are increased; in the elevated plus maze test (EPM) behavior in the open arm was activated. However, if a dose of 5.2 µg/kg induced the rat behavior with signs of agitation (increased exploratory motor activity in the light–dark box and EPM tests, and motor activity with frequent visits to different boxes or arms and exploratory activity in the light–dark box and EPM tests), then a dose of 52 µg/kg, on the contrary, inhibited a number of behavioral responses, which was expressed in increased anxiety (increased the freezing in the open field and EPM) and in increased the latency of entry into the closed arm of the EPM. It is assumed that SWCNTs in small doses, when injected intranasally into the brain of rats, can dose-dependently disrupt the structural and functional state of nervous tissue cells and/or cause neuroinflammation in the structures involved in the mechanisms of anxiety and related conditions, as a result, the behavior of rats in tests for anxiety also changes in a dose-dependent manner.

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.

The unique properties of carbon nanotubes (CNT) (increased strength, flexibility, electrical and thermal conductivity) make them very promising for use in various fields of human activity. But the question of their toxic effects on the body is actively discussed in the literature. There is a lot of body toxicity data of large doses of CNT, but the question of the potential danger of small doses of CNT is a practically unexplored issue. Earlier, we showed that a single intranasal injection of single-walled CNT (SWCNT) in a small dose (4 μg / kg) to rats inhibited the mRNA production of most cytokines in both spleen and brain. At the same time, the expression of the early c-fos gene in the olfactory bulb and the pyriform cortex was increased [Loseva E.V. et al., 2016]. It is known very little about the effect of low doses of SWCNT on animal behavior. The aim of this study was to investigate the effect of a small doses of SWCNT with subacute intranasal administration of different duration on the behavior of rats in the elevated plus-maze (EPM) test, which is used to estimate the anxiety. Male Wistar rats were daily intranasal administrated 100 μl of SWCNT suspensions in physiological saline (PS) in small (5.2 μg / kg, n = 9) dose for 4 (n = 9) or 13 (n = 9) days. Control rats were administrated analogically 100 μl of PS (n = 19). A statistical analysis of indicators of rats' behavior in EPM (5 minutes each) was performed using Kruskal-Wallis one-way analysis of variance, and then using the comparison on the non-parametric criterion of Mann-Whitney for independent features by the program STATISTICA 7.0. It was shown that in the EPM test in rats after 4-fold injection of a small dose of SWCNT, as compared with the control group, there was observed the behavior activation in the center and open arm, what was expressed in frequent and lengthy visits, but with a reduction of the average time of such visits. These animals also had increased the vertical exploratory activity (rears), horizontal exploratory activity (head dips) and motor activity, but the grooming indicators were decreased. After chronic administration of SWCNT in a small dose for 13 days, the direction of some of these changes was maintained, but was expressed to a much lesser degree (only at the level of the tendency in comparison to the control group). So, these rats, compared with the control, more often and longer visited the central site, more often visited open arms and less time were in closed arms. At the same time, the average time of the dark visits was smaller, and the average time of grooming, on the contrary, was longer than in the control. Thus, the intranasal administration of SWCNT in a small dose for 4 days in rats had provoked atypical symptoms of anxiety, which were expressed in an agitated behavior in the EPM, as evidenced by the strong activation of most behavioral reactions. The intranasal administration of SWCNT in a small dose for 13 days also has led to some activation of behavior or atypical anxiety, but it was expressed to a much lesser extent than with the acute injection of SWCNT. There wasn't observed an increasing of agitated behavior or a cumulative negative effect of SWCNT during chronic intranasal injection. We can suggest that nanotubes when administered in a small dose for 4 days can penetrate cells and their organelles, causing damage and death of tissue structures, in particular, when they penetrate into the brain, which leads to agitated behavior. At the same time, with subacute administration of SWCNT in a small dose during 13 days, protective reactions can gradually develop, leading to accelerated utilization of nanotubes, for example, by macrophages and astrocytes, which can absorb them, that leads to a diminution of the activation of behavior. To test this assumption, special morpho-functional studies are required.

The density of cartilage cells (chondroblasts) proliferating on a silicon substrate coated with vertically oriented arrays of multi-walled carbon nanotubes (MWCNTs) was shown to be higher than on a pure silicon substrate. Electron microscopy showed that the cells in a nutrient medium affected the vertical position of the nanotubes in the array. A method for structuring the MWCNT arrays by 100-ns laser pulse scanning and abrasive water processing on planar substrates was developed. As a result of the structuring of the MWCNTs, the arrays become resistant to bending under the influence of the nutrient medium with mesenchymal stem cells. Structured MWCNT arrays were shown to have no toxic or pathological effect on the viability and morphology of stem cells. Thus, such materials can be suggested for use in cell-adhesive components of biomedical devices.

Introduction . Lack of antiviral drug forms in ophthalmology stimulates to study the efficacy of drugs of other pharmacological groups with potential antiviral activity. Adenoviral eye infections are widespread and highly contagious. Material and methods. The antiviral effect of the drug was estimated by changing the DNA titer of the virus in adenovirus-infected cells, controlling. the specificity of the viral affection by setting PCR in real time. The cytotoxic effect of Vitabact ® was studied on Vero cell culture. Results. Installations of the preparation according to the treatment scheme (after infection of the culture) resulted in 2.7-fold decrease in the viral DNA amount. When Vitabact ® was injected into cells in dilution of 1/128 (the first dilution of the drug that does not refuse the cytotoxic effect on Vero cells) according to the prophylactic scheme the level of adenovirus replication decreased by 1.7 times. Conclusions . The preparation of pycloxidine had the maximum antiviral effect in the treatment scheme mode. This circumstance opens the perspective of specifying the spectrum and mechanisms of antiviral effect of pixloxidine and makes it possible to use Vitabakt as a component of the second stage (starting from 10–12 day of the disease) of empirical therapy of viral conjunctivitis.

Методом времяпролетной масс-спектрометрии вторичных ионов (ToF-SIMS) исследованы изменения состава плазматических мембран (ПМ) фибробластов эмбриона человека под воздействием наноразмерных анионов кремний-молибденовой кислоты (КМК). Измерены и интерпретированы зависимости масс-спектров основных липидов ПМ от концентрации КМК, коррелирующие с их послойными распределениями и со сродством холестерина к фосфолипидам. Обнаружен новый для биохимии клетки эффект – значительное снижение относительного содержания в ПМ холестерина и сфингомиелина под воздействием многозарядных анионов гетерополикислоты (ГПК). Для водных растворов КМК при концентрации С ~ 10мкМ/л и периода воздействия 48 ч обнаружено, что количество холестерина в ПМ снижается в 2–2.5 раза, при этом количество сфингомиелина уменьшается на 20–25%. Предложен новый механизм начального воздействия ГПК на плазматические мембраны, сводящийся к селективному травлению многозарядными анионами. Согласно предлагаемому механизму на первом этапе взаимодействия аниона полиоксометаллата с клеткой осуществляется экстракция из ПМ холестерина и сфингомиелина – основных регуляторов проницаемости и микровязкости ПМ. Как следствие возросшей проницаемости ПМ в клетках возможно ускорение жизненно важных трансмембранных и латеральных процессов.

This paper reports a study of the inhibitory and immunomodulating activity of phosphoric and silicon heteropoly acids with Keggin anions ([ХМ(1)12 – nМ(2)nО40]–m, where X = P, Si; M = Мо, W, and V; m = 3, 4, 5) toward human embryonic fibroblast cells using MTT and polymerase chain reaction techniques. The correlation between the inhibitory activity of heteropoly acids and their anion charge has been shown and interpreted.