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Introduction. Rotavirus infection causes more than 250 million episodes of acute gastroenteritis annually, of which approximately 130,000 cases in children under 5 years of age are fatal. In this regard, the search for drugs for the treatment of rotavirus infection seems extremely relevant.The aim of the research was to evaluate the antiviral activity of Cytovir®-3 against human rotavirus on a cellular infection model.Material and methods. The objects of the study were a mixture of active ingredients and individual components, identical in composition and ratio, contained in Cytovir®-3. The study was carried out using a monkey kidney cell culture MA-104 and a laboratory strain of human group A rotavirus — 568, genotype G3P. Cultural, virological, molecular biological and statistical methods were used during the study.Results and discussion. Analysis of the survival of MA-104 cells in the presence of Cytovir®-3 showed that in the concentration range from 100 to 200 µg/ml, the drug reproducibly exhibited antiviral activity, which was expressed in increased cell survival compared to the viral control. Cytovir®-3 in a non-toxic concentration of 150 µg/ml suppressed the reproduction of rotavirus by 1.0-2.0 lg СC₅₀/ml with various schemes of introduction into cell culture at all periods of observation, which was accompanied by a significant decrease in the concentration of viral RNA and a cytoprotective effect.

Introduction. Due to the ability of the influenza virus to mutate, it is necessary to constantly search for new drugs with preventive and direct antiviral effects.The aim of the study is to investigate the protective antiviral properties of the drug Thymogen®, a dosed nasal spray, on a model of lethal influenza pneumonia in laboratory animals.Material and methods. White mature mice were selected for the experiment on the antiviral activity of the tested drug samples against H1N1 influenza virus; the mice were divided into the following groups (30 animals each): two negative control groups; two groups receiving Thymogen®, a dosed nasal spray (before and after infection); one group of animals received Tamiflu®, and one received Hexoral®. The mortality of animals with influenza pneumonia was assessed; histological and morphometric analyses were also carried out.Results and discussion. The morphological picture of the lungs of animals correlated with their protective activity when analyzing the survival of animals. The normalization of tissue structure was pronounced the most in the group of animals infected with the virus, pre-incubated with Thymogen®, a dosed nasal spray, and in the group receiving Tamiflu®. Moreover, the viral load in the lungs was lower by 1.5 and 1.2 orders of magnitude in the group receiving Thymogen®, dosed nasal spray, compared to the negative control group (the 3rd and the 6th days of the experiment, respectively), which corresponds to a decrease in the intensity of viral reproduction by 31.6 and 15.8 times

Introduction. The requirements of modern clinical guidelines for the treatment of respiratory viral infections suggest the possibility of identifying a specific viral pathogen. In this regard, the search for drugs with selective activity against respiratory syncytial virus and parainfluenza virus is relevant. The purpose of the work is to study the antiviral activity of the drug Cytovir®-3 in vitro in relation to the cytopathogenic effect of respiratory viruses (parainfluenza virus and respiratory syncytial virus). Material and methods. The antiviral effect of Cytovir®-3 in comparison with Umifenovir against parainfluenza virus and respiratory syncytial virus was studied on Vero cell culture. Drugs were administered 1 hour before (prophylactic regimen) and 1 hour after (treatment regimen) infection of the cell culture with respiratory viruses. The working range of concentrations of the studied drugs was calculated based on the values of 50% cytotoxic concentration calculated based on the results of a quantitative microtetrazole test. Results and discussion. The drug Cytovir®-3 in two schemes of application (therapeutic or prophylactic) showed its antiviral efficacy in vitro against respiratory syncytial virus and parainfluenza virus due in the non-toxic range (0–794 µg/ml). At the same time, the suppressive effect of the drug Cytovir®-3 against the parainfluenza virus begins at lower concentrations of the drug with its early (preventive) introduction into cell culture (250 mcg/ml). Conclusion. Antiviral activity of Cytovir®-3 has been proven in vitro against parainfluenza virus and respiratory syncytial virus. At the same time, in all series of experiments, Cytovir®-3 had a higher index of selectivity of antiviral action than that of the comparison drug Umifenovir.

The ongoing coronavirus disease (COVID-19) pandemic over the past three years has caused close attention to the problem of herd immunity, which is understood as: "resistance to the spread of a contagious disease within a population or herd". Collective immunity is formed both as a result of infection (natural spread of the pathogen in a population of susceptible individuals) and as a result of the use of specific vaccines. During the COVID-19 pandemic, both mechanisms for the formation of collective immunity were realized. In the first wave, there was a natural formation of collective immunity to the virus following recoveries from COVID-19 caused by pandemic spread of SARS-CoV-2. Starting from December 2020, the widespread use of specific vaccines against SARS-CoV-2 began in the USA, Great Britain, China, Russia, and a number of other countries. This launched the process of post-vaccination collective immunity formation; its features have depended on the vaccine types implemented. Currently, in those countries where vaccination and revaccination of recovered patients is widely carried out, immunity is "hybrid" in nature. Several commonalities should be noted in the pandemic experience: a somewhat regular, periodic (wavelike) nature of the COVID-19 epidemic process; changes in pathogen genetics in variants in all countries; and expansive mass vaccination programs in many populations. From these, we can draw some conclusions about the general trend for all countries in the formation of collective immunity during the pandemic: At the beginning of the pandemic in 2020, overall population seroprevalence did not exceed 20%. Other findings were: the highest seroprevalence rates were noted in the children's age group; pronounced regional differences were revealed; and the highest indicators were noted among medical workers. Collective immunity developed as a result of infection or illness, and in the majority of seropositive volunteers, it was represented by antibodies to both antigens. At the height of the pandemic in the summer of 2021, population seroprevalence reached 50%. This was due to both a significant number of convalescents and the start of mass vaccination campaigns. In all countries, specific differences in seroprevalence (by age, region, profession) leveled out, leading to more uniformity. During this period, the formation of "hybrid" immunity is clearly prominent, and the proportion of individuals with antibodies to RBD alone increased (due to vaccination with vector vaccines). Later, mass vaccination, as well as involvement of most of the population in the epidemic process due to the emergence of the highly contagious Omicron strain, raised the level of collective immunity to 80-90%. This led to a sharp decrease in COVID-19 incidence in the second half of 2022 in all countries participating in the study. In the later stages of the pandemic (2022-2023), almost 90% of seropositive volunteers had hybrid immunity, reflected as antibodies to both antigens (Nc, RBD).

Despite all efforts of the world community, the COVID-19 pandemic remains one of the main epidemiological challenges of our time. Even with its widespread distribution, the infection may have certain local features due to social, geographic, and climatic factors. Objective: to study collective immunity to SARS-CoV-2 in the population of the Republic of Tajikistan.A cross-sectional, randomized study of herd immunity was carried out according to a program developed by Rospotrebnadzor and the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The ethics committees of the corresponding entities approved the study: Tajik Ministry of Health and Social Protection; and the St. Petersburg Pasteur Institute (Russia). Based on questionnaire results, 4,022 people were selected, representing 0.15% (95% CI: 0.14-0.15) of the total population randomized by age and region. In subsequent laboratory analysis, 3682 people took part. The distribution and quantitative content of antibodies (Abs) to viral nucleocapsid (N Ag) and receptor binding domain (RBD Ag) were determined by ELISA. When questioned, a history of SARS-CoV-2 vaccination was indicated by 69.7% (95% CI: 68.2-71.2) of the volunteer cohort. Vector vaccines were most frequently used (50.6%; 95% CI: 48.7-52.5), with whole-virion inactivated preparations in second place (23.0%: 95% CI: 21.4-26.6) and mRNA vaccines in third place (21.0%; 95% CI:19.4-22.6).The cohort (n = 3682) featured 27.5% men and 72.5% women. The overall seroprevalence was 98.5% (95% CI: 97.7-99.2) in men and 99.4% (95% CI: 99.0-99.6) in women (differences statistically insignificant). Overall seroprevalence in the cohort was 99.2% (95% CI: 98.8-99.4) and ranged from 97.2 to 100% in certain subgroups. Asymptomatic seropositivity in the whole cohort was 98.4% (95% CI: 97.6-99.1). As a result of a mandatory vaccination program introduced in Tajikistan under a COVID-19 Emergency Project, the level of herd immunity among vaccinated individuals reached 99.5% (95% CI: 99.1-99.7), which is similar to the level reached in the cohort as a whole.The epidemic situation that developed in Tajikistan by mid-March 2022 was characterized by an almost absolute level of herd immunity, as evidenced by an absence of detected overt COVID-19 cases since the end of February (2022).

Introduction. The first pandemic in the 21st century, caused by the pathogenic representative of the coronavirus SARS-CoV-2, began in the Chinese city of Wuhan, where the first outbreak of coronavirus pneumonia was recorded in December 2019. The disease spread so quickly around the world that already on February 11, 2020, WHO was forced to declare a pandemic of the “coronavirus disease 2019” COVID-19. The first case of COVID-19 in the Stavropol Territory was registered on March 20, 2020, and three weeks later, starting from the 15th week of the year, a steady increase in the incidence began, which lasted until the 52nd week. During the study period, the incidence increased from 21.1 to 28.3 per hundred thousand of the population. Growth 1.3 times.Purpose: to determine the dynamics of population immunity among the population of the Stavropol Territory in 2020-2021. during the period of an epidemic increase in the incidence of COVID-19. Materials and methods. The SARS-CoV-2 study was carried out according to a unified methodology within the framework of the program for assessing the population immunity of the population of the Russian Federation, developed by Rospotrebnadzor with the participation of the St. Pasteur. In total, 2688 people were examined, divided into 7 age groups. In the examined individuals, the level of specific IgG to the SARS-CoV-2 nucleocapsid was determined by the enzyme immunoassay.Results. The level of seroprevalence among residents of the Stavropol Territory was 9.8%. The largest proportion of seropositive individuals was found in the age groups 1-6 and 7-13 years old (19.2% and 19.7%, respectively). Seroprevalence had no gender differences and ranged from 9.3% to 10.8%. When assessing the distribution of the proportion of seropositive persons in different geographic territories of the region, it was found that the maximum proportion was found in the Kochubeevsky district (23.1%), the minimum in Kislovodsk (7.7%). Among convalescents, the content of specific antibodies to SARS-CoV-2 was noted in 73.3%, which is 7.8 times higher than the average population level. When conducting seromonitoring in the 2nd half of 2020, a 10-fold increase in seroprevalence was recorded, accompanied by a decrease in incidence from the 5th week of 2021. Among asymptomatic volunteers in whom SARS-CoV-2 RNA was detected by the polymerase chain reaction, antibody titers to viruses were found in 78.6%, which corresponds to the seroprevalence of convalescents. The proportion of seropositive persons among those who have come into contact with COVID-19 patients was 16.4%, (1.8 times higher than the average for the population). Out of 262 seroprevalent volunteers, the asymptomatic form of SARS-CoV-2 was detected in 92% of the examined, which indicates a significant role of the number of asymptomatic forms of infection in the epidemic process of COVID-19.Conclusion. The results of assessing the population immunity of the population of the Stavropol Territory indicate that it has not yet reached the threshold level at which a decrease in the intensity of the COVID-19 epidemic process can be expected.

Objective was to investigate the SARS-CoV-2 collective immunity status of the population of Belarus within the context of the COVID-19 pandemic. Materials and methods. The work was carried out according to the methodology for assessing SARS-CoV-2 population immunity, developed by Rospotrebnadzor Russia and the Ministry of Health of Belarus with the participation of the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The Bioethics Committee of Belarus and the local ethics committee of the St. Petersburg Pasteur Institute approved the study. Selection of participants was carried out using a questionnaire method and online technology (internet, cloud server). Volunteers were randomized into seven age groups (years of age): 1–17; 18–29; 30–39; 40–49; 50–59; 60–69; and 70+. Regional randomization ensured proportional representation of volunteers from each region, and no more than 30 people were included from one enterprise. In accordance with manufacturer instructions, blood plasma samples were analyzed for: IgG antibodies (Abs) to the SARS-CoV-2 nucleocapsid (Nc) using a quantitative ELISA test system; and IgG Abs to the receptor binding domain (RBD) of the SARS-CoV-2 S (spike) surface glycoprotein using a qualitative ELISA test system. Statistical processing was carried out using Excel 2010 and other software. Statistical differences were designated as significant when p < 0.05, unless otherwise indicated. Results. The level of seroprevalence, in terms of Abs to Nc among the Belarusian population, was 38.4% (95% CI 37.6–45.4). The highest Ab levels were found among individuals in older age groups (50-70+ years old). The lowest were found in children 1–17 years old and in young people 18–39 years old The distribution of seroprevalence across Belarusian regions was relatively homogeneous, with the exception of the Minsk Region, where a statistically significant decrease in the indicator was noted. In terms of profession, the largest share of seropositive individuals was found among transportation workers; the smallest was found in business. The moderate COVID-19 incidence has not led to a dramatic increase in the number of contacts. The base reproduction number (R0) was 1.3. In the Republic of Belarus, there was a moderate level of asymptomatic COVID-19 among seropositive individuals (45.3% [95% CI 44.0–46.7]). This form of infection was observed most often among children aged 1–17 years old (65.0% [95% CI 61.3–68.6]). In parallel with seroprevalence assessment, SARS-CoV-2 vaccination was carried out. We used two vaccines: Gam-COVID-Vac (also known as Sputnik V, developed by Gamaleya National Center for Epidemiology and Microbiology, Russia); and BBIBP-CorV (Sinopharm, PRC). Vaccination against SARS-CoV-2 was accompanied by an increase in the level of anti-RBD Abs (95% [95% CI 94.7–96.7]). Taking into account the vaccination of a subset of the population with BBIBP-CorV, the overall herd immunity, inferred from the analyzed indicators (presence of anti-Nc or anti-RBD Abs), was 47.1% (95% CI 46.3–48.0). Conclusion. COVID-19 in Belarus was characterized by a moderately pronounced course of the epidemic process. The threshold level of herd immunity to SARS-CoV-2 has not yet been reached, as a result of which the conditions for progression of the epidemic remain.

The aim: to study the structure and dynamics of population immunity to SARSCoV-2 of the population of the Southern Regions of the Far East (SRFE): Khabarovsk, Primorsky Krai and Amur Region during the COVID-19 epidemic in 2020.Materials and methods. The work was carried out according to the program for assessing population immunity to SARS -CoV-2 of the population of the Russian Federation according to the methodology developed by the Rospotrebnadzor with the participation of the St. Petersburg Pasteur Institute. The study was approved by the ethical committee of the St. Petersburg Pasteur Institute. The selection of participants was carried out by a questionnaire method using cloud technologies. The volunteers were randomized by age by stratification into 7 age groups: 1–17, 18–29, 30–39, 40–49, 50–59, 60–69, 70+ years old. Territorial randomization consisted in limiting the engaging of volunteers – no more than 30 people from one enterprise. After the initial cross-sectional study, a 3-stage seromonitoring was carried out, in which the same volunteers participated. Antibodies to the SARS-CoV-2 nucleocapsid were determined in peripheral blood serum by the enzyme immunoassay using an appropriate set of reagents produced by the State Scientific Center for Medical and Biological Sciences of the Rospotrebnadzor (Obolensk). Statistical analysis was performed using the Excel package. The confidence interval for the proportion was calculated using the A. Wald, J. Wolfowitz method with A. Agresti, B.A. Coull’s correction. The statistical significance of the differences was calculated online using a specialized calculator. The statistical significance of the differences was assessed with a probability of p˂ 0.05, unless otherwise indicated.Results. In a comparative analysis, the highest morbidity was observed in the Khabarovsk Territory, the lowest – in the Primorsky Territory. The level of seroprevalence among the population of the region was 19.6 % (95 % CI: 18.2–21.1) in the Khabarovsk Territory, 19.6 % (95 % CI: 18.1–21.2) in the Primorsky Territory19,6 % and 45,5 % (95 % CI: 43.7–47.3) in the Amur region. The highest seroprevalence was noted among 1–17 years old children, mainly due to the subgroup of 14–17-years-olds. The smallest proportion of seropositive was found among 40–49-year-olds in the Khabarovsk Territory (14.7 %, 95 % CI: 11.2–18.6), 18–28-yearolds in the Primorsky Territory (13.3 %, 95 % CI: 10.0–17.1) and 30–39-year-olds in the Amur Region (36.3 %, 95% CI: 31.7–41.6). No statistically significant dependence of seroprevalence on territorial and occupational factors has been established, with the exception of an increase in the proportion of seropositive medical workers in Primorsky Territory. In the process of 3-stage seromonitoring, a regular increase in the proportion of seropositive people was revealed in all SRFE. The resulting tendency is correctly described by a second-order polynomial. A relationship was revealed between the number of convalescents and persons in contact with them, which made it possible to calculate the base reproductive number (R0) in the range from 1.4 (Primorsky Territory) to 2.4 (Amur Region). Analysis of seroprevalent volunteers showed that the number of asymptomatic individuals varied from 94.1 % (95 % CI: 92.8–95.3) to 98.3 % (95 % CI: 98.8–99.2). This indicates that most of the volunteers had COVID-19 asymptomatically.Conclusions. A comparative study showed the prevalence of seroprevalence in the Amur Region compared with the Khabarovsk and Primorsky Territories. The relationship between the number of convalescents and persons in contact with them was noted. The value of the base R0 is calculated. It has been shown that more than 90 % of seropositive individuals in the COVID-10 SRFE were asymptomatic.

Aim. To determine the level of SARS-CoV-2 seroprevalence among the Novosibirsk Region population against the background of the COVID-19 pandemic. Material and methods. The work was carried out in 2 phases: 1) a cross-sectional cohort study performed 28.06– 15.07.2020; 2) longitudinal cohort 3-stage seromonitoring: 1st stage 28.06–15.07.2020; 2nd 14.09–04.10.2020; 3rd 10–30.12.2020 The work was carried out according to a unified methodology developed by Rospotrebnadzor with the participation of St-Petersburg Pasteur Institute, taking into account the recommendations of the WHO. IgG antibodies to the SARS-CoV-2 nucleocapsid protein were detected by ELISA using a kit of reagents produced by the SRCMSB (Obolensk) according to the manufacturer’s instructions. Statistical analysis was performed using Microsoft Excel 2010 and other programs. Results. The seroprevalence in the region’s population was 9.1% (95% CI 8.0–10.2): maximum in children 14–17 years old (17.6%, 95% CI 12.3–23.9) and persons over 75 years (14.8%, 95% CI 11.4–18.8), minimum among persons 30–39 years old (4.9%, 95% CI 3.0–8.0). Increased rate was noted among the unemployed (15.4%, 95% CI 9.9–17.1) and other individuals (13.0%, 95% CI 8.6–18.5). Seroprevalence was 33.3% (95% CI 16.3–59.0) in COVID-19 convalescents and 19.0% (95% CI 13.9-25.0) in contact persons. More than 94.7% (95% CI 91.2–97.2) of seropositive individuals were asymptomatic. During the serological monitoring, seroprevalence increased from 7.4% (95% CI 6.2–8.9) at 1st stage 1 to 12.4% (95% CI 10.6–14.3) at 2nd , and 31% (95% CI 28.8–33.3) at 3rd stage. Conclusion. SARS-CoV-2 herd immunity has not reached the threshold level, this does not exclude exacerbation of the epidemic process.

On account of the COVID-19 pandemic, the global pharmaceutical industry has achieved impressive results in the development and introduction of various types of vaccines causing the formation of acquired immunity against the SARS-CoV-2 coronavirus into clinical practice. However, none of them currently show the declared one hundred percent guarantee of protection. In the case of the COVID-19 disease, patients with concomitant pathologies are the most vulnerable to the occurrence of severe complications. The aerosol route of transmission of SARS-CoV-2 contributes to the emergence of outbreaks of the new coronavirus infection in crowded places and closed rooms with poor ventilation. In this regard, an urgent problem is the search for drugs with local antiviral activity, which, together with restrictive measures and mask wearing policy, can potentially reduce the likelihood of contracting coronavirus. In this experimental in vitro study on Vero CCL81 cell culture (ATCC), the local antiviral activity of the drug Thymogen® spray against the SARS-CoV-2 virus was studied in comparison with the antiseptic Miramistin® solution. As a result of the experiment, no toxic effects on Vero cells were detected in the drugs in the studied concentrations. In a series of experiments, Thymogen® spray showed local antiviral activity against SARS-CoV-2 when the virus titer was 5,2 lg TCID50. Therefore, the drug Thymogen® dosed nasal spray has high potential as a topical drug for prevention and treatment of COVID-19 disease, which requires additional confirmation in relevant clinical studies.

Introduction. The COVID-19 pandemic has stimulated the search for drugs with specific antiviral activity against the new pathogenic strain of the SARS-CoV-2 coronavirus. First of all, scientific search was aimed at studying drugs with already proven efficacy against influenza and ARVI. The aim of this work was to study the antiviral activity of Cytovir®-3 in vitro in relation to the cytopathogenic effect of the SARS-CoV-2 virus. Material and methods. The antiviral activity of the drug Cytovir®-3 against the SARS-CoV-2 virus was studied in experimental models in vitro on Vero CCL81 cell culture (ATCC). The maximum tolerated concentration and the 50% cytotoxic dose were determined using a quantitative microculture tetrazolium test assay to calculate the working range of the concentrations of the test drug. Results and discussion. As a result of the study, it was shown that the greatest activity of the drug was manifested when it was added to the cells 24 hours before and 1 hour and 24 hours after viral infection, the inhibition level reached 53% (>IC50) at the drug concentrations of 105, 55, and 85 µg/ml, respectively. Cytovir®-3 suppressed the viral activity of SARS-CoV-2 in the dose range from 10 µg/ml to 105 µg/ml under the indicated infection conditions. It was found that the drug did not exhibit cytotoxic effects on the Vero cell culture in the range of antiviral doses. Conclusion. The antiviral activity of Cytovir®-3 against the SARS-CoV-2 virus has been proven due to the achievement of IC50, which is below the maximum tolerated dose of 149 µg/ml.

Purpose. Determination of the SARS-CoV-2 population humoral immunity among the population of the Krasnoyarsk Territory during the COVID-19 epidemic.Materials and methods. The study was carried out as a part of project for assessing population immunity to SARS-CoV-2 among the population of Russian Federation using unified methodology developed by Rospotrebnadzor, with the participation of the Research Institute for Epidemiology and Microbiology named by Pasteur, and taking into account the recommendations of the WHO. The work involved 2907 volunteers, selected by the online survey and randomization by age and territory. All volunteers were divided into 7 age groups: 1–17, 18–29, 30–39, 40–49, 50–59, 60–69, 70 and older (70+), including a total 246–449 people. Population immunity testing was carried out during the formation of groups (1st stage), and then twice more, with the interval of 6–8 weeks. Serum was obtained from venous blood samples obtained from volunteers, in which antibodies to the SARS-CoV-2 nucleocapsid were determined by the enzyme immunoassay. The results were analyzed by methods of nonparametric statistics: median, interquartile range, rank correlation coefficient were calculated in the Excel statistical package. The confidence interval to seroprevalence indicators (95% CI) was calculated using the WinPepi statistical package (version 11.65). The statistical significance of the differences was assessed with a probability level of p ≤ 0.05.Results. The seroprevalence of the population of the Krasnoyarsk Territory during the 5-month period of seromonitoring had increased 3.3 times from 12.8% (95% CI 11.3–14.4) to 41.7% (95% CI 39.4–4.0) , while the grouping by age had not revealed any peculiarities throughout the study. The trend towards a decrease in the incidence was formed on the 6th week of 2021. The seroprevalence of convalescents after COVID-19 during the initial testing was 61.5% (95% CI 40,6–79.8), among those who were in contact with patients with COVID-19 or convalescents –23.8% (95% CI 13.9–36.2) . Among the volunteers, 347 seropositive persons were identified, 324 of which were observed asymptomatic course.Conclusion. The structure of the population humoral immunity to SARS-CoV-2 of he population of the Krasnoyarsk Territory has been investigated. It was found that an increase in seroprevalence to 41.7% (95% CI 39.4–4.0) was accompanied by a decrease in morbidity.

Relevance. At the end of 2019, the world was confronted with a novel coronavirus (SARS-CoV-2), In January 2020, WHO declared an epidemic related to SARS-CoV-2, a health emergency of international importance, and in March characterized the spread of the world. diseases like a pandemic.Purpose of the study. Conduct a comparative analysis of the seroprevalence of the population of the Sverdlovsk and Chelyabinsk regions – the largest administrative territorial entities of the Middle and Southern Urals – against the backdrop of the COVID-19 pandemic.Materials and methods. The work was carried out under the program of the first stage of assessing the seroprevalence of the population of the Russian Federation according to a unified methodology developed by Rospotrebnadzor of the Russian Federation with the participation of the Saint Petersburg Pasteur Institute. The selection of participants was carried out by the method of questioning and randomization. The presence of antibodies to the SARS-CoV-2 nucleocapsid was determined in blood serum by the enzyme immunoassay.Results. Comparative analysis of the results showed that the incidence rate of COVID-19 in the Chelyabinsk region was consistently lower, and the seroprevalence at the first stage of the study was statistically significantly higher (p

The novel coronavirus (SARS-CoV-2) pandemic, dubbed COVID-19, has become one of the most serious challenges for human populations in the vast majority of countries worldwide. Rapid spreading and increased mortality related to it required new approaches to manage epidemic processes on a global scale. One of such approaches was based on analyzing SARS-CoV-2 seroprevalence associated with COVID-19. Our aim was to summarize the results on assessing seroprevalence to the SARS-CoV-2 nucleocapsid antigen (Nc) in residents from 26 regions of the Russian Federation, carried out during the first wave of the COVID-19 epidemic.Materials and methods. Seroprevalence distribution was examined in 26 model regions of the Russian Federation according to the unified method developed by the Rospotrebnadzor with the participation of the Federal State Institution Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology. Such approach implied formation of a group of volunteer subjects in model geographic region who were tested by ELISA for anti-Nc serum antibody level in peripheral blood. Analyzed primary data obtained in separate regions were either accepted for publication or released.Results. The current paper finalizes the data obtained in all 26 regions of the Russian Federation. The total SARS-CoV-2 seroprevalence was 19.5 (10.0–25.6)% with the maximum and minimum value found in the Kaliningrad Region and the Republic of Crimea, respectively (50.2% vs. 4.3%). A pattern of age-related seroprevalence distribution indicates insignificant predominance of seroprevalence among subjects of 1–17 years old: 22.1 (13.1–31.8)%. Among COVID-19 convalescents positive for SARS-CoV Nc antibodies it reached 60.0 (40.0–73.3)%. The number of contact persons comprised 6285 subjects or 8.5% of total volunteer cohort, with the level of seroprevalence reaching up to 25.3 (17.95–35.8)%. A direct correlation was revealed between levels of seroprevalence in convalescent and contact volunteers. In addition, the reproductive number for SARS-CoV was calculated comprising 5.8 (4.3–8.5) suggesting that one convalescent subject can infect at least 4 healthy individuals. A high level of asymptomatic forms of COVID-19 among seropositive subjects was confirmed empirically comprising up to 93.6 (87.1–94.9)%.Conclusion. A single cross-sectional study performed during 2020 June–August timeframe allowed to assess pattern of sex- and agerelated COVID-19 seroprevalence for general population in 26 Russian Federation regions. The data obtained may serve as a basis for the longitudinal cohort investigation with serial subject sampling. The timing and duration of study will be determined by dynamics of ongoing COVID-19 epidemic.

Introduction. The coronavirus disease (COVID-19) pandemic was announced by WHO in February 2020. In the Khabarovsk Krai, the first three cases of the disease were diagnosed on March 19, 2020, these cases were imported from Argentina (transit through Italy). The epidemic process of COVID-19 in the Khabarovsk Krai is characterized by a slow increase in the incidence. During the period of time when the SARS-CoV-2 seroprevalence study was conducted the incidence rates varied from 35.9 to 39.1 per 100 thousand population. Within the next 5 weeks the incidence continued to increase, the maximum level was 67.3 per 100 thousand population. A statistically significant decrease in the incidence is noted in the first decade of August. The study of the SARS-CoV-2 seroprevalence among residents of the region was carried out from June 9 to June 21, 2020 during the period of increasing intensity of the epidemic process of COVID-19 infection.Aim. To determine the level and structure of herd immunity to SARS-CoV-2 virus among the population of the Khabarovsk Krai during the period of intensive spread of COVID-19.Materials and methods. The study was conducted as a part of the first stage of a large-scale Rospotrebnadzor project to assess the herd immunity to SARS-CoV-2 virus among the population of the Russian Federation, taking into consideration the protocol recommended by WHO. The selection of volunteers for the study was carried out by the method of questionnaires and randomization by random sampling. The results of a survey of 2675 individuals were included into analysis. The number of volunteers in all age groups was similar.Results. The results of the study showed that the herd immunity to SARS-CoV-2 in the total population of the Khabarovsk Krai was 19.6%. The maximum level of herd immunity was observed in children 14–17 years old (34.4%), children 7–13 years old (24.8%), and people over 70 years (22.6%). The highest level of seropositivity, except for the children and the elderly, was found among educational workers (26.7%). The lowest level of seropositivity was found in the military (8.7%) and the unemployed (8.3%). There were no statistically significant differences in the level of seroprevalence between men and women.Conclusions. The results of the seroepidemiological study demonstrated that in the Khabarovsk Krai, the presence of the contacts with COVID-19 patients is associated with the 1.4-fold increase in the likelihood of the seroconversion. Antibodies were detected in 58.9% of the past COVID-19 cases. In individuals with the previous positive PCR test result, antibodies were detected in 50% of cases. A high rate of asymptomatic infection, up to 93.7%, was observed among seropositive volunteers.

The first reports about HIV (human immunodeficiency virus) were appeared to the 1980s. By 2017 more than 37 million people were living with HIV. Human papilloma virus (HPV) is universally spread, with some estimates showing that about 1% of the sexually active population having genital warts. Human papilloma virus (HPV)-induced infection frequently accompanies the clinical course of HIV and can manifest itself in a full spectrum of clinical-pathologic forms ranging from common warts to malignant neoplasia. Due to the widespread use of antiretroviral therapy, the number of patients with a combined infection (HIV+HPV) is steadily increasing. Here we review current clinical treatment options for HPV manifestations. High-dose antiretroviral therapy does not impede HPV treatment, and can even improve its efficacy in some cases. The topical administration of imiquimod, an immune response modifier, is an effective conservative treatment in HIV-infected patients with HPV. The immunomodulation therapy of imiquimod can serve as an effective alternative of aggressive chemical and mechanical procedures. Maximum efficacy with the lowest replaces rates may be expected from combined use of mechanical ablation methods with a subsequent follow up treatment with imiqui-mod. The best therapeutic result is expected in HIV-positive patients who are received high-dose antiretroviral treatment. The advantages of Vartocid, the modified Russian equivalent of the generic imiquimod.

The global community is experiencing one of the largest infectious disease outbreaks in the 21st century. In the Saratov Region, the first case of new coronavirus infection was confirmed on March 19, 2020.The maximum increase in cases was noted between May 15 and June 30, during that time the total number of infected people in the region increased from 1526 to 6444. Since July 2020, a stable incidence level of new coronavirus infection has been observed in the Saratov Region, without a steady decline.The aim of the study was to assess the status of population immunity to the SARS-CoV-2 virus among residents of Saratov and the Saratov Region under the COVID-19 epidemic.Materials and methods. In the period from June 23 to July 26, 2020, a serological study of blood samples from 3372 volunteers of different age groups was conducted. The content of antibodies to SARS-CoV-2 was determined by ELISA using a set of reagents “ELISA anti-SARS-CoV-2 IgG” produced by the State Scientific Center of Applied Microbiology and Biotechnology of the Rospotrebnadzor (Russia).Results and discussion. In general, the incidence of COVID-19 in the Saratov Region is taking place against the background of moderate seroprevalence to the SARS-CoV-2 virus, accompanied by a high incidence of non-apparent (asymptomatic) forms of the infectious process. The absence of clinical symptoms of the disease, in the context of the limited use of methods for determining the RNA of the SARS-CoV-2 virus in PCR (11 % of the region’s population) makes it difficult to assess the real spread of the virus in the population and to establish the timing of the formation of persistent herd immunity. A low rate of antibody response among individuals with a positive result of PCR analysis, as well as among volunteers who had an infection in May, June 2020, indicates a weak formation of the immune response, or the prevalence of individuals reacting mainly by activating the cellular link of the immune system in the population. The obtained results, although they need to be explained in a number of respects, can be applied to the organization of preventive measures, including vaccination, in the region.

By August 2020, more than 850000 cases of new coronavirus infection (COVID-19) caused by SARSCoV-2 were confirmed in the Russian Federation, with the Rostov Region as one of the ten most affected regions in Russia. The spread of the disease is largely determined by the state of population immunity in a certain area. Our research focuses on specific humoral immune response and estimates the level of herd immunity to SARS-CoV-2 virus among the population of the Rostov Region.Materials and methods. The study involved 3,048 people; the volunteers participating in the study were divided into seven age groups. The content of antibodies to SARS-CoV-2 was determined applying ELISA using a kit for the analysis of human serum or blood plasma for the presence of specific IgG to the nucleocapsid of the SARS-CoV-2 virus, manufactured by the State Scientific Center of Applied Microbiology and Biotechnology (Obolensk) in accordance with the instructions for use.Results and discussion. The assessment of seroprevalence to SARS-CoV-2 in the Rostov Region showed that the proportion of people positive for IgG to the new coronavirus was 16.5 %, the range of seropositive individuals in the general population was between 13.9 % and 19.1 % (p

Introduction. The COVID-19 pandemic was announced by WHO in February 2020. In the Kaliningrad region, the first case (imported) was registered in early March 2020, the beginning of the epidemic increase fell on the 14th week. 2020, and the peak incidence was reached in the 22nd week of the year, after which there was a steady decrease in the number of cases. The study of population immunity was carried out at the 32nd week during the period of the lowest level of intensity of the epidemic process.Purpose of the study. Assessment of the assessment of the level of population immunity to the SARS-CoV-2 virus among the population of the Kaliningrad region during the period of the epidemic incidence of the population of COVID-19.Materials and methods. The study was carried out as part of the first stage of the Rospotrebnadzor program to assess population immunity to SARS-CoV-2 among the population of the Russian Federation. The selection of volunteers for the study was carried out by a questionnaire survey and subsequent randomization. The analysis includes the results of a survey of 2675 people. The number of volunteers in age groups ranged from 314 to 493 people. The results obtained were processed by the methods of variation statistics.Results. The results obtained showed that the average seroprevalence in the population was 50.2%, while the highest seroprevalence was found in the child age group 1-17 years (66.9%) and among persons aged 18-29 (57.0). No significant gender differences were found (men – 48,3 ± 1,6%, women – 51,1 ± 1,1%). The distribution of the proportion of seropositive people in the settlements of the region varied from 33,9% to 59.6%. The largest share of seroprevalence in the representative samples was found among people engaged in art / creativity (55,3%), the smallest – among educational workers (42,0%). Among COVID-19 convalescents, the level of humoral immunity reached 94,6%. Most of the seropositive volunteers (95,2%) did not have any symptoms of COVID-19, that is, they belonged to the category of asymptomatic carriers.Output. The results of a survey of a representative cohort of volunteers in the Kaliningrad region showed that they are characterized by a high level of population immunity, which makes it possible to expect a decrease in.

In late 2019, there were reports of an outbreak of infection caused by a new strain of beta coronavirus SARSCoV-2, the WHO identified the disease as coronavirus disease 2019 (COVID-19). In Tatarstan, the first case of COVID-19 was diagnosed on March 16, 2020, it was an imported case from France. The period of increase in the incidence lasted during the 12th to the 19th week, when the highest rate was recorded, amounting to 16.7 per 100 thousand population. Subsequently, a statistically significant decrease in the incidence was noted. Seroprevalence study was conducted at week 27 (8th week of decline of morbidity).The purpose of the seroepidemiological study was to measure the level and to identify the structure of herd immunity against the SARS-CoV-2 virus among the population of the Republic of Tatarstan during the rapid spread of the COVID-19 outbreak.Materials and methods. The selection of volunteers for the study was carried out by the method of questionnaires and randomization by random sampling. The exclusion criterion was active COVID-19 infection at the time of the survey. 2,946 people were examined for the presence of specific antibodies to SARS-CoV-2. The age of the surveyed volunteers ranged from 1 year to 70 years and older.Results. The results of the study showed that in the Republic of Tatarstan during the period of COVID-19 incidence, there was a moderate seroprevalence to SARS-CoV-2, which amounted to 31.3%, against the background of a high frequency (94.5%) of asymptomatic infection in seropositive individuals who did not have a history of past COVID-19 disease, positive PCR result and ARVI symptoms on the day of the examination. The maximum indicators of herd immunity were established in children aged 7–13 years (42.0%), children 14–17 years old (40.3%), with a simultaneous decrease in seroprevalence in persons aged 70 and older (24.0%). In different regions of the Republic of Tatarstan, there was a wide variation in seropositivity results from the minimum in the Zainsky district (8.6%) to the maximum in the Arsky district (74.3%). In 21 out of 38 surveyed districts, the results were unrepresentative due to the small sample size. In COVID-19 convalescents, antibodies are produced in 83.3% of cases. In persons with a positive result of the PCR analysis carried out earlier, antibodies were detected in 100% of cases. Among the volunteers who had contact with patients with COVID-19, the proportion of seropositive is 37%Conclusion. The dynamics of seroprevalence among the population of the Republic of Tatarstan can be qualified as positive, the results obtained can be used to develop a forecast for the development of the epidemiological situation, as well as to plan measures for specific and non-specific prevention of COVID-19.

The first case of COVID-19 was diagnosed in St. Petersburg on March 2, 2020; the period of increase in the incidence lasted for 10 weeks, the maximum rates were recorded in mid-May, and subsequently there was a statistically significant decrease in the incidence.Objective: to determine the level and structure of community immunity to SARS-CoV-2 among the population of St. Petersburg during the period of intensive spread of COVID-19.Materials and methods. Selection of volunteers for the study was carried out through interviewing and randomization. The exclusion criterion was active COVID-19 infection at the time of the survey. 2713 people aged 1 to 70 years and above were examined for the presence of specific antibodies to SARS-CoV-2. Antibodies were detected by enzyme immunoassay.Results and discussion. Studies have shown that in St. Petersburg, in the active phase of COVID-19 epidemic, there was a moderate seroprevalence to SARS-CoV-2, which amounted to 26 %, against the background of a high frequency (84.5 %) of asymptomatic infection in seropositive individuals who did not have a history of COVID-19 disease, positive PCR result and ARI symptoms on the day of examination. The maximum indicators of herd immunity were established in children 1–6 years old (31.1 %), 7–13 years old (37.7 %) and people over 70 years old (30.4 %). Differences in the level of seroprevalence in the age groups of 18–49 years are statistically significant. The highest level of seroprevalence was found among the unemployed (29.7 %), healthcare workers (27.1 %), education sector (26.4 %) and business sector personnel (25 %). In convalescents, COVID-19 antibodies are produced in 75 % of cases. In individuals with positive result of PCR analysis carried out earlier, antibodies are detected in 70 % of the cases. The results of the study of herd immunity to SARS-CoV-2 are essential to forecast the development of the epidemiological situation, as well as to plan measures for specific and non-specific prevention of COVID-19.

Objective of the seroepidemiological study was to determine the level and structure of herd immunity to SARS-CoV-2 among the population of the Irkutsk Region during the period of an increase in the incidence of COVID-19.Materials and methods. The content of antibodies to SARS-CoV-2 was determined by ELISA applying a reagent panel “ELISA anti-SARS-Cov-2 IgG” produced by the State Scientific Center of Applied Microbiology and Biotechnology (Obolensk).Results and discussion. The investigation has revealed that the herd immunity of the total population of Irkutsk Region amounted to 5.8 %. The greatest share of seropositive persons was among the children aged 14–17 (13.8 %) and 1–6 (11.8 %). It has been established that the risk of infection increases by 3.1 times in case of contact with COVID-19 patients. After exposure to COVID-19, antibodies were produced in 56.5 % of the cases. The share of asymptomatic forms among seropositive residents of the Irkutsk Region reached 81.2 %. Consequently, during the chosen period of increased COVID-19 incidence among the population of Irkutsk Region low level of seroprevalence was formed. A significant proportion of asymptomatic forms of infection characterize high intensity of the latently developing epidemic process. The results obtained can be used when organizing preventive measures, including vaccination, and for forecasting morbidity rates.

The first case of COVID-19 was registered in the Leningrad Region on March 13, 2020. The period of increasing intensity of the epidemic process lasted 8 weeks. One month after reaching the maximum incidence rate, a study was organized to determine seroprevalence to COVID-19 among the population of the Region.Objective of the study was to determine the level and structure of community immunity to SARS-CoV-2 virus in the population of the Leningrad Region in the period of intensive COVID-19 transmission.Materials and methods. The work was carried out within the framework of the Rospotrebnadzor project on assessment of community immunity to the SARS-CoV-2 virus in the population of the Russian Federation. The content of antibodies to SARS-CoV-2 was determined applying ELISA using a kit for the analysis of human serum or blood plasma for the presence of specific IgG to the nucleocapsid of the SARS-CoV-2 virus , manufactured by the State Scientific Center of Applied Microbiology and Biotechnology (Obolensk) in accordance with the instructions for use.Results and discussion. The study has showed that the herd immunity of the population of the Leningrad Region was 20.7 %. The maximum level has been established in children 1–6 years old (42.3 %) and people over 70 years old (29.0 %). The highest level of seropositivity, except for children and older people, was found among the unemployed (25.1 %). The lowest level of seroprevalence was detected in civil servants (12.8 %) and military personnel (16.7 %). It has been shown that the risk of infection increases by 1.5 times in case of contacts with COVID-19 patients. After exposure to COVID-19 virus, antibodies are produced in 82.1 % of the cases. In individuals with a positive PCR test result obtained earlier, antibodies are detected in 82.8 % of cases. The share of asymptomatic forms among seropositive residents of the Leningrad Region was 86.9 %. The results of assessing the herd immunity to SARS-CoV-2 in the population of the Leningrad Region indicate that during the period of intensive COVID-19 transmission, an average level of seroprevalence was formed. A significant proportion of asymptomatic forms of infection characterizes the high intensity of the latently developing epidemic process. The results obtained should be taken into account when organizing preventive measures, including vaccination, and predicting morbidity rates.

Here we review means of immunomodulatory therapy for coronavirus infection caused by SARS-CoV-2 (COVID-19). It has been appreciated that highly limited arsenal of relatively effective means and methods of prevention and treatment of the COVID-19 pandemic is available. The goal of our study was to analyze some therapeutic approaches based on available publications for COVID-19 treatment viewed from acting via innate immunity system. Convalescent plasma serotherapy represents one of the means with verified therapeutic efficacy that was accompanied with decreased viral load and relief of the disease symptoms. The drawback of serotherapy results from limited number of potential plasma donors and profound variety in amount of SARS-CoV-2-specific antibodies found in donor plasma. Another approach to COVID-19 therapy is based on using monoclonal antibodies engineered to target specific virus antigenic determinants, most often surface spike antigen. Antibodies blocking such antigen are able to prevent virus entrance into target cells and development of overt infection. On the other hand, there are monoclonal antibodies abrogating production or binding of excessive amounts of pro-inflammatory cytokines, such as IL-6, TNFα, etc., some of which (tocilizumab) have been already tested in COVID-19 therapy, whereas the remaining preparations are being currently investigated and tested. A certain breakthrough in COVID-19 therapy was provided by the well-known drugs chloroquine and dihydrochloroquine, which have proven to be effective as antiviral, anti-inflammatory and immunomodulatory means. Finally, a new multicomponent immunomodulatory preparation Cytovir-3 has been proposed already passed clinical trials and recommended for use in prevention and treatment of influenza and SARS and might have found its own niche in preventing COVID-19, as SARS-CoV-2 also belongs to the group of acute respiratory viruses. Thus, the arsenal of means for COVID-19 prevention and treatment contains the drugs for immunomodulatory therapy and prevention of immune-related disorders developing in response to invasion pathogenic viruses and lowering a risk of possible damage. Hence, correct and scientifically justified use of such remedies will increase overall effectiveness of fight against the coronavirus pandemic.

Coronaviruses (CoVs) comprise a polymorphic group of respiratory viruses causing acute inflammatory diseases in domestic and agricultural animals (chicken, pig, buffalo, cat, dog). Until recently, this infection in humans was mainly observed during the autumn-winter period and characterized by a mild, often asymptomatic, course. The situation changed dramatically in 2003, when SARS outbreak caused by pathogenic CoV (SARS-CoV) was recorded in China. A decade later, a new CoV outbreak occurred in the form of the Middle East respiratory syndrome (MERS-CoV), whereas in December 2019, SARS-CoV-2 (COVID-19) cases were recorded, which transformed within the first months of 2020 into the pandemic. In all three cases, CoV disease led to severe bronchopulmonary lesions, varying from dry, debilitating cough to acute respiratory distress syndrome (ARDS). At the same time, multiple changes in innate immunity were noted most often manifested as a pronounced inflammatory reaction in the lower respiratory tract, featured by damaged type II pneumocytes, apoptosis, hyalinization of alveolar membranes, focal or generalized pulmonary edema. Destructive processes in the respiratory tract were accompanied by migration of monocytes/macrophages and granulocyte neutrophils to the inflammatory focus. Such events were accompanied by production of pro-inflammatory cytokines, which magnitude could ascend up to a cytokine storm. SARS-CoV is characterized by symptoms of secondary immunosuppression, manifested by the late onset of interferon production and activation of NLRP3 inflammasomes – the key inflammatory factor. The reason for such reaction may be accounted for by CoV arsenal containing extensive set of structural and non-structural proteins exerting pro-inflammatory and immunosuppressive properties. Delayed IFN production allowed CoV to replicate actively and freely, and when type I IFN synthesis was eventually triggered, its activity was detrimental and accompanied by an aggravated infection course. Thus, SARS can surely be referred to immune-dependent infections with a marked immunopathological component. The purpose of this review was to describe some mechanisms underlying formation of innate immune response to infection caused by pathogenic coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19).

Aim: To compare the safety and prophylactic efficacy of Cytovir-3 and Arbidol in an open-label randomized clinical trial in children at seasonal risk of infectious respiratory disease.Methods: This study was performed in the period preceding a seasonal outbreak of acute respiratory viral infections (ARVI) and influenza. The study enrolled apparently healthy children aged 6 to 18 years without contra-indications to either Cytovir-3 or Arbidol. Cytovir-3 was given as 1 capsule per day, each day in a fasted state for 12 days. Arbidol was taken as a 100 mg capsule twice a week for three weeks. Following dosing, subjects were followed-up for a further three weeks. Overall health and presence of symptoms of either ARVI or influenza were monitored daily in all subjects. The level of sIgA in saliva was baselined before treatment and measured at the end of the follow-up period.Results: Most subjects did not exhibit any change in overall health status during the dosing and follow-up periods. The first two cases of illness in subjects receiving Cytovir-3 were diagnosed at the end of the third week after completion of dosing. In those subjects receiving Arbidol the first cases of illness were reported at the end of the second week following the end of prophylactic dosing. All patients displayed a significant increase in sIgA level at the end of the dosing period, but this was more pronounced in the Cytovir-3 group. Conclusion: The results of this comparative randomized clinical trial confirmed the safety and tolerability of both medications, and that the prophylactic efficacy of Cytovir-3 is equal to that of Arbidol.

This paper investigates a formal approach which supports a critically significant step in object oriented analysis and software engineering. It is proposed to create an object class structure model based on an Ontological Data Analysis. Pragmatically important attributes and Ontological Data Analysis basic stages review is given.

Abstract. Ascorbic acid (vitamin C, AA) is an essential nutrient of the human diet due to its participation on numerous regulatory and enzymatic processes. AA takes part in such vital physiological processes as hormone production, collagen synthesis, stimulation of the immune system, etc. In the present review the activities of AA are considered that provide its protective effect at influenza infection. This effect can be result of direct virus-inhibiting activity of AA as well as of anti-inflammatory and antioxidant properties. Oxidative stress during influenza infection leads to nonspecific damage of the pulmonary tissue and subsequent inflammation of the lungs. The antioxidant activity of AA results in alleviation of infection due to suppression of tissue damage as well as in inhibition of reactive oxygen species-mediated signal transduction and regulatory reactions. After oxidation by ROS, AA is converted to dehydroascorbic acid (DAA) and inhibits the key enzymes of NF-κB pathway, such as kinases IKKα and IKKβ. AA itself blocks the activity of another component of the NF-kB pathway, kinase IKKβ(SS/EE), whose activity is directed to the phosphorylation of the factor IκBα. As a result, activation of NF-κB and its transport to the nucleus does not occur. Thus, AA performs a dual function: first, it neutralizes free radicals, preventing them from activating NF-κB, and secondly, the product of its oxidation, DAA, further blocks the activation of this pathway. In addition, in some cases AA results in the decrease in the infectious activity of influenza virus that is not due to the antioxidant activity of AA, but to direct virus-inhibiting activity. Taken together, the presented data suggests that the use of drugs with antiviral and antioxidant activity, as a combination of individual drugs or, as in the case of AA, as a single drug with complex activity, for treatment of influenza has advantages over the etiotropic drug monotherapy scheme.

Background. Imiquimod is an imidazole derivative acting as an immunomodulator on the level of innate and adaptive immune system. Our objective was to evaluate the antiviral activity of generically reproduced imiquimod administered subcutaneously in mice and intravaginally in guinea pigs against herpes simplex virus (HSV), as well as to study the dynamics of serum interferon (IFN) synthesis under different dosing regimens. Results. When administered subcutaneously at doses of 0.5, 1.0 and 10 mg/kg imiquimod increased IFN production in mice in a dose-dependent manner with maximum serum IFN concentrations occurring 4 hours after dosing. Imiquimod protected mice from intraperitoneal HSV infection at doses of 3.2 and 32 LD50.The utmost protection (100% survival) was observed when imiquimod was administered at a dose of 100 mg/kg daily for 5 days before infection. Topical application of imiquimod 5% cream exhibited significantly more rapid and complete virus elimination in guinea pigs intravaginally infected with HSV type 2 compared to control group. Conclusion. Imiquimod produced as a generic possesses the same immunomodulatory and antiviral properties as the originally synthesized substance.

The article presents the results of clinical studies on the comparative effectiveness of different forms of the drug Cytovir-3 (syrup and powder for solution for oral administration) and Immunal l in the treatment of acute respiratory viral infections in children. It was found in a comparative randomized parallel-group study of 90 children aged two through six years that the drug Cytovir-3 (syrup and powder) became active faster than the comparison drug Immunal, providing normalization of body temperature, reduction of some manifestations of the general intoxication and respiratory syndrome, as well as elevated levels of serum immunoglobulin A. All drugs in the study had an equally normalizing effect on the content of peripheral blood leukocytes and erythrocyte sedimentation rates. The compared products were characterized by good tolerability, lack of side effects and high preventive efficacy against respiratory disease complications. Cytovir-3 drugs (syrup and powder for oral solution) and Immunal had similar ratios of clinical and laboratory safety, efficacy and tolerability. Both products can be used for the treatment of respiratory diseases in children aged two through six years.

Influenza is a highly contagious human disease. In the course of use of antiviral drugs drug-resistant strains of the virus are formed, resulting in reduced efficiency of the chemotherapy. The review describes the biological activity of glycirrhetinic (GLA) and glycirrhizic (GA) acids in terms of their use as a therapeutic agent for viral infections. So, these compounds are against a broad spectrum of viruses, including herpes, corona-, alphaand flaviviruses, human immunodeficiency virus, vaccinia virus, poliovirus type I, vesicular stomatitis virus and influenza A virus. These data indicate that anti-viral effect of these compounds is due to several types of activity — direct antiviral effects, effects on cellular proand anti-viral and immunomodulating pathways, in particular by activation of innate immunity system. GA interferes with early steps of the viral reproductive cycle such as virus binding to its receptor, the absorption of the virus by endocytosis or virus decapsidation in the cytoplasm. This is due to the effect of GA-induced reduction of membrane fluidity. Thus, one mechanism for the antiviral activity of GA is that GA molecule increases the rigidity of cellular and viral membranes after incorporation in there. This results in increasing of energy threshold required for the formation of negative curvature at the fusion zones, as well as difficult lateral migration of the virus-receptor complexes. In addition, glycyrrhizin prevents interaction of viral nucleoprotein with cellular protein HMGB1, which is necessary for the viral life cycle. Glycyrrhizin also inhibits the induction of oxidative stress during influenza infection, exhibiting antioxidant properties, which leads to a reduction of virus-induced production of cytokines/chemokines, without affecting the replication of the virus. A wide spectrum of biological activity and effect on various aspects of the viral pathogenesis substantiate the effect of GA and GLA as a component of a complex antiviral therapy. A combination of antiviral mechanisms makes GA and GLA unique means capable of providing an antiviral effect in many types of viral pathologies that emphasizes their prospects as a component of comprehensive antiviral therapy. Further research in the field of optimization of their application may lead to the development of new antiviral drugs and effective schemes of their combined application.

Аbstract. Influenza is a highly contagious infection of humans. The use of specific antivirals leads to emergence of drug-resistant strains following by the decrease of efficacy of ethiotropic chemotherapy. In this review the data about the decrease of the level of viral replication and severity of pathological process based on the use of alternative targets of cellular instead of viral origin are presented. The medicines for decreasing the production of proinflammatory cytokines (eritoran), restricting the degranulation of mast cells (ketotifen), inhibitors of cyclooxygenases (celexocib, mesalasine, SC-560), inhibitors of sphingosine-1-phospate pathway (AAL-R) and compounds increasing the capillars stability by strengthe ning the contacts between endothelial cells (Slit protein) have been described in the review. The special attention is paid to the inhibitors of cellular pathways that are used by the virus to provide its reproduction, such as NF-κB, Raf/MEK/ERK, PI3K/AKT/mTOR. Information concerning anti-influenza activity of kinase and autophagy inhibitors is summarised as well as data about the preparations of combined mechanism of activity — glycirrhizic acid and dipeptide alpha-glutamyl-tryptophane. Further studies in the field of search and optimization of inhibitors of cellular components as remedies against influenza infection could lead to the development of novel antivirals with high efficacy, broad spectrum of activity and low probability of virus resistance.

Non-linear time-sequences of fracture-related events were studied in drifting sea-ice and fracturing rock. A reversible drop of the b-value was detected prior to the large-scale sea-ice cover fragmentation, when the time sequence of impact interactions between ice-fields was fully decorrelated. A similar loss of the temporal invariance of the fracture process was revealed in the time sequence of microfracture events detected in a loaded rock sample. These temporal gaps in the continuous critical state of the considered self-organizing, open systems were attributed to the property of hierarchicity inherent in the geophysical objects. A combination of scaling and hierarchic features in the behavior of fracturing solids manifests itself in the heterogeneity of the temporal pattern of fracture process.