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There is a danger that a natural smallpox virus may be reintroduced from the unknown spring or that a similar virus with the same pathogenic properties may appear or that somebody may create a synthetic copy of such a virus. That is why it is crucial to have a proper laboratory pattern that may imitate a natural smallpox disease and other human orthopoxviruses. A rabbitpox virus may provoke a grave and highly contagious disease in rabbits with a high death rate. The symptoms of this disease in rabbits is similar to symptoms of natural smallpox in humans. There have been no cases of rabbitpox in humans.Purpose of the study – To summarize data on research of a rabbitpox virus and to analyze the symptoms of this disease in rabbits that is similar to a natural pox virus in humans. This analysis may contribute to the development of new drugs against smallpox.Study base sources – English scientific papers available on the Internet.Method of the study – Analytical.Results and discussion. Rabbitpox was first detected in 1930 in lab. rabbits in Utrecht, the Netherlands, then in the USA, at Rockfeller University in New York. From 1941 the outbreaks of rabbitpox were registered in research institutes in Europe and in the USA. However, there were no cases of this disease in rabbits in the wildlife. The analysis has demonstrated that the pattern “a rabbit–a rabbitpox virus” has been quite successful in pre-clinical studies of protective efficiency of orthopoxvirus vaccines, monoclonal antibodies, mRNA-based drugs and chemotherapeutic agents (thiosemicarbazone, Cidofovir, tecovirimat, Brincidofovir, etc.) for different transmission modes including inhalative one. This pattern is also useful for evaluation of diagnostic sets, employed for orthopoxviruses detection.Conclusion. Pattern “a rabbit–a rabbitpox virus” is safe for humans and is promising for simulation of different pathological states when we conduct various medical and biological studies of orthopoxvirus infections. It also may be used to evaluate the efficiency of immunobiological drugs against smallpox, chemotherapeutic agents and diagnostic sets.

INTRODUCTION. Climacteric syndrome is characterized by significant disorders in the nervous, musculoskeletal, urinary and cardiovascular systems in women of the perimenopausal and postmenopausal periods. The main reason is a sharp decrease in estrogen levels. Menopausal hormone therapy is often used for treatment, but due to contraindications and complications, it does not always completely solve the problem. This has sparked interest in alternative treatments such as dry carbon dioxide baths. AIM. To study the effectiveness of using dry carbon dioxide baths in women with menopausal syndrome and evaluate their impact on the neurovegetative, metabolic and psycho-emotional state of these patients. MATERIALS AND METHODS. A prospective randomized study was conducted involving 70 patients with moderate climacteric syndrome aged from 48 to 60 years. Using a simple randomization method, the women were divided into 2 groups: 35 patients of the main group received 10 procedures of dry carbon dioxide baths with a CO2 concentration of 15–20 %, temperature 28–32 °C, lasting 15–20 minutes, 35 patients of the control group did not receive any treatment. To assess the effectiveness of treatment, a modified Kupperman-Uvarova menopausal index, an assessment of the effect of “hot flashes” on daily life on the HFRDIS scale, as well as daily blood pressure monitoring (SMAD) were used. RESULTS AND DISCUSSION. After treatment, patients in the main group observed a significantly significant (p 0.05) improvement in the patients’ condition in the form of a decrease in integral indicators of the modified menopausal index and an assessment of the impact of hot flashes on daily activity on the HFRDIS scale by 28.2 and 43.1 %, respectively, as well as in the form of a decrease in average daily systolic blood pressure by 13.7 %. CONCLUSION. The use of dry carbon dioxide baths is recommended for use in women with moderate climacteric syndrome, since this method significantly improves the quality of life of patients and is an effective non-drug that can reduce the drug load on the body of a woman suffering from neurovegetative disorders.

INTRODUCTION. Recently, alternative methods of treating patients with menstrual disorders have become increasingly in demand. One of these methods is hydrotherapy, which has a complex effect on the body. AIM. To evaluate the effectiveness of contrast baths and underwater shower-massage as part of complex treatment of women with polycystic ovary syndrome. MATERIAL AND METHODS. A prospective randomized study was conducted in 120 women with polycystic ovary syndrome, grade 1 obesity, and menstrual irregularities. During the study, 2 groups were allocated by randomization: the first (main) included 60 patients, whose treatment included a special diet and a 24-day course of hydrotherapy, consisting of a single daily intake of fresh water contrast baths (12 days), alternating every other day with underwater shower-massage procedures (12 days). The second group, the control group, was represented by 60 patients who received only a special diet. RESULTS AND DISCUSSION. After treatment, a significantly significant decrease in body mass index was noted in both groups of the study (by 4.9 % in the control group and by 11.3 % in the main group). In women receiving a course of hydrotherapy, there was an improvement in lipid and carbohydrate metabolism with a decrease in the atherogenic index by 36.1 % and an insulin resistance index by 31.0 %, as well as an improvement in indicators of psycho-emotional state, characterized by a decrease in situational anxiety on the Spielberger Hanin scale (p 0.05) and improvement in overall mood on the “Well-being, activity, mood” scale (p 0.05). CONCLUSION. Based on the results of the study, it was proven that the use of hydrotherapy in complex treatment programs for women with polycystic ovary syndrome is an effective and safe method that can be included in standard treatment regimens for this condition.

Abrogation of obligatory vaccination against smallpox has lead to degradation of herd immunity and humanity has become vulnerable to long known infections, such as monkeypox (mpox), cowpox, camelpox, buffalopox and emerging ones, caused by viruses Alaska and Akhmeta. This situation demands availability of safe smallpox vaccines, the immunogenicity of which is comparable to vaccines used in the period of smallpox elimination. The aim of this review is to analyze the research of Japanese scientists on the production and investigation of properties of the smallpox vaccine LC16m8 and to assess further prospects for the use of the LC16m8 strain. The LC16m8 vaccine was obtained based on one of the Lister clones and has been licensed in Japan since 1975. Whole-genome sequencing revealed that its main difference from the genome of the original strain is a mutation in the B5R gene, which determines its safety for laboratory animals and humans. The immunogenicity of the vaccine based on this strain is comparable to the immunogenicity of the first generation vaccines: Lister, Dryvax, Ikeda. According to WHO recommendations, second generation vaccines ACAM 2000 and third generation vaccines based on the LC16m8 strain are reserve drugs. However, the established fact that the LC16m8 strain, when passaged in cell culture, spontaneously reverts to the original variant of the Lister strain led to genetic engineering work to delete the B5R gene to obtain the LC16m8Δ mutant, which is not capable of reversion. A vaccine based on the LC16m8Δ strain could technically be classified as a fourth generation drug, and taking into account the high immunogenicity and relative safety of this strain based on the results of preclinical studies, there is a real prospect of producing an advanced and effective reserve drug based on it. Thus, analysis of long-term data on the study of the LC16m8 vaccine indicates that this drug is superior to other analogues of the 1st, 2nd and 3rd generation in terms of effectiveness and safety. Further genetic engineering work with this strain, which made it possible to obtain a safe but immunogenic genovariant of the LC16m8Δ strain, is a clear example of a productive movement towards the development of safe and effective fourth generation vaccines.

One of the promising areas for improving laboratory diagnostics is the active introduction of next-generation sequencing (NGS), which retains the key advantages of molecular tests and allows the detection of a wide range of diverse microorganisms. Despite the significant advantages of NGS in the laboratory diagnosis of infectious diseases, there are also a number of objective obstacles to its widespread use.The purpose of the work is to consider existing hardware and software solutions for whole-genome sequencing, as well as the prospects and problems of their implementation in the practice of the RCB protection troops of the Armed Forces of the Russian Federation for the identification of pathogens of various etiologies.The source base of the research includes an analysis of data published in domestic and English-language scientific publications, as well as posted on the Internet.The research method is analytical.Results. Materials are presented that summarize data on three generations of sequencing technologies, their advantages and disadvantages. It is shown that with the development of NGS technologies, many technical problems arise that need to be deeply analyzed and solved. Despite its great potential, NGS has not yet been widely adopted in clinical microbiology laboratories, partly due to the lack of standardized workflows.Conclusions. For the successful use of NGS by units of the RCB protection troops of the Armed Forces of the Russian Federation, it is necessary to solve the main problem, which is the development of domestic hardware, appropriate bioinformatics tools and databases certified in accordance with the established procedure for functioning offiine without connecting to the Internet.

In the last 10 years, scientists' interest in the horsepox pathogen has increased sharply due to the obtaining of its chimeric copy and the discussion of whether it was used to create early smallpox vaccines and the dangers of technologies that allow the restoration of extinct pathogens of dangerous infections.The aim of the work is to summarize the materials on modern studies of the horsepox virus.The source base of the study is English-language scientific literature available via the Internet.The research method is an analysis of scientific sources on horsepox from the general to the specific. We considered the area of distribution of the virus, its epidemiological danger, phylogenetic relationship, data on the sequencing of the horsepox virus genome and the likelihood of its use in the creation of the first vaccines, as well as obtaining its chimeric copy, on the basis of which a new smallpox vaccine was created – TNX-801.Results and discussion. The horsepox virus belongs to the poxvirus family, the orthopoxvirus genus. Classical horsepox has previously been reported only in Europe (France), Mongolia, and Kenya. The complete nucleotide sequence of the horsepox virus genome MNR-76 isolated in Mongolia has been determined. In addition to genes common to all orthopoxviruses, it includes intact genes specific only to this virus, the homologues of which are fragmented in the genome of other orthopoxviruses. Phylogenetic analysis of a number of orthopoxviruses was performed and a phylogenetic tree was constructed based on the conserved central region of the genome and some of the more variable terminal regions. The data obtained indicate that horsepox virus is most closely related to vaccinia virus and rabbitpox virus strains. Although horsepox is currently considered extinct, its pathogen may persist in unknown reservoirs. The data on the sequencing of the horsepox virus genome, strain MNR-76, suggest that horsepox virus could have served as the basis for the first smallpox vaccines. A chimeric copy of the horsepox virus was obtained using synthetic biology, which was used to create a new smallpox vaccine, TNX-801. On its basis, a recombinant vaccine against SARS-CoV-2 was constructed. The restoration of "extinct viruses" using synthetic biology methods has led to intense debates about the benefits and risks of such research.Conclusion. It cannot be ruled out that the use of modern genetic engineering technologies may lead not only to the development of effective vaccines, but also to the production of new orthopoxviruses pathogenic for humans and animals, or to the reintroduction of smallpox, which is especially dangerous in the context of the virtual absence of smallpox immunity in the population and international control over experiments in the synthetic biology of dangerous pathogens.

Discontinuation of vaccination after the completion of Smallpox global eradication program led to a sharp decrease in the level of collective immunity not only to smallpox but also to other orthopoxvirus infections. Over the past 10–15 years, the world has seen an increase in the frequency of diseases caused by smallpox viruses of cows, buffaloes, camels. The outbreak of mpox (a disease caused by the monkey pox virus) occurred in 2022–2023. Analysis of the literature data on the organization of the orthopoxvirus genome suggest that smallpox could have occurred in the past as a result of evolutionary changes in the zoonotic progenitor virus. In this regard, there is a threat of a new particularly dangerous anthropozoonosis, the pathogen of which can occur both naturally and artificially. The aim of the review is to analyze open science published data on aerobiological research with OPVs conducted by the U.S. Department of Defense from 1994-2013, which was a period of restricted research and storage of smallpox virus samples. The authors did not find any publications of the results of aerobiological research with orthopoxviruses conducted by the US Department of Defense after 2013 in open scientific sources. The review presents a data analysis in Russian and English-speaking scientist publication as well as those posted on the Internet. The presented results of aerobiological studies with orthopoxviruses indicate the interest of the US military department in carrying out experimental work of dual use, including monitoring of the properties of orthopoxviruses and a possible change in their pathogenicity for humans, selection of optimal laboratory models for studying the properties of orthopoxviruses, and the possibility of modeling the properties of the smallpox virus when using other orthopoxviruses (cowpox virus, rabbit pox virus, monkey pox virus), modeling of the main characteristics of the disease caused by the smallpox virus in humans and evaluation of the effectiveness of existing and newly developed vaccines against smallpox, comparative study of effectiveness of antiviral drugs for regular or post-exposure prophylaxis of naturally occurring smallpox and monkey smallpox.

The basis for criteria of the taxonomic classification of DNA and RNA viruses based on data of the genomic sequencing are viewed in this review. The genomic sequences of viruses, which have genome represented by double-stranded DNA (orthopoxviruses as example), positive-sense single-stranded RNA (alphaviruses and flaviviruses as example), non-segmented negative-sense single-stranded RNA (filoviruses as example), segmented negative-sense single-stranded RNA (arenaviruses and phleboviruses as example) are analyzed. The levels of genetic variability that determine the assignment of compared viruses to taxa of various orders are established for each group of viruses.

Lassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) based on the lineage IV Josiah strain protected 100% of cynomolgus macaques against heterologous challenge with lineage II and III strains of LASV when therapy was initiated beginning at day 8 after challenge. LASV strains from Benin and Togo represent a new lineage VII that are more genetically diverse from lineage IV than strains from lineages II and III. Here, we tested the ability of Arevirumab-3 to protect macaques against a LASV lineage VII Togo isolate when treatment was administered beginning 8 days after exposure. Unexpectedly, only 40% of treated animals survived challenge. In a subsequent study we showed that Arevirumab-3 protected 100% of macaques from lethal challenge when treatment was initiated 7 days after LASV Togo exposure. Based on our transcriptomics data, successful Arevirumab-3 treatment correlated with diminished neutrophil signatures and the predicted development of T cell responses. As the in vitro antiviral activity of Arevirumab-3 against LASV Togo was equivalent to lineage II and III strains, the reduced protection in macaques against Togo likely reflects the faster disease course of LASV Togo in macaques than other strains. This data causes concern regarding the ability of heterologous vaccines and treatments to provide cross protection against lineage VII LASV isolates.

Background. The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, originated in Wuhan, China, has claimed millions of lives around the world. In this regard, the search for effective drugs, including the repurposing of existing ones, has become an urgent task. A promising treatment strategy appears to be drug disruption of viral reproduction. RNA-dependent RNA polymerase (RdRp) is the central subunit of the RNA synthesis process for all positive-strand RNA viruses and is therefore an attractive target for antiviral inhibitors.The aim of this work is an experimental study of the antiviral activity of various drugs based on 6-fluoro-3-hydroxy-2-pyrazinecarboxamide (Favipiravir) in vitro and in vivo against the SARS-CoV-2 coronavirus (COVID-19).Material and methods. The experiments were carried out on a permanent culture of African green monkey kidney cells — Vero Cl008. The effectiveness of the drugs was assessed by suppressing the reproduction of the virus in vitro. Biological activity was assessed by titration of the virus-containing suspension in Vero Cl008 cell culture by the formation of negative colonies. Syrian golden hamsters orally infected with the SARS-CoV-2 virus, variant B, were used in the study. The effectiveness of the drug was assessed by the coefficient of therapeutic action.Results. The results of the study revealed that the compounds FP-1 and Avifavir in the concentration range of 100–400 µg/ml almost completely suppress the reproduction of the SARS-CoV-2 virus; the CTI index for the drug FP-1 was 4, for Avifavir it was 2. The ED₅₀ value for FP-1 was 26 µg/ml, for Avifavir it was 36 µg/ml. Preparations T-705 and Coronavir revealed antiviral activity only at extremely high concentrations. The CTI was 1. During the study on Syrian golden hamsters orally infected with the SARS-CoV-2 virus, variant B, at a dose of 5×105 PFU, it was shown that the use of Avifavir and FP-1 has a high protective efficacy, while Coronavir and T-705 cause a moderate suppression of virus reproduction in the target organ. According to the complex of clinical-virological, biochemical, and hematological indicators, the disease severity index (DSI) and the therapeutic index (TI) were calculated. For the drug Avifavir, the DSI was 0.269; the TI was 71.3% with a probability of 99.9%.Conclusion. Of the studied compounds, Avifavir and FP-1 showed the highest antiviral activity.

Abstract The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers (P

Relevance. After smallpox eradication, in conditions of population immunity to orthopoxviruses absence, Monkeypox virus became most significant orthopoxvirus, pathogenic for humans. Therefore the generalization of data on the areas of infection outbreaks, human diseases and methods of prevention and treatment of monkey pox is important task. Aim. To characterize the problem of monkeypox in the world based on an analysis of foreign scientific publications over the past 20 years. Materials and methods. The work used publications presented in the main international medical information databases PubMed, Web of Science, Embase, etc. To analyze the publications, the analytical epidemiological method was used. Results and discussion. Monkeypox virus, obtained and identified in 1958, by genetic and phenotypic differences divides on two clades: West-African with lethality 3.6% and Central-African (Congo Basin) with lethality 10%. Monkeypox virus transmission to men happens in two ways, either from animal-to-human or human-to-human. Monkey pox is endemic only on African continent, but In 2003 year the first outbreak, numbering 47 confirmed cases, was occurred in non-endemic country – USA and the largest monkeypox outbreak began in Nigeria in September 2017 year and continue to the present. Comparison of the genome sequences of strains, isolated from patients in non-endemic countries, showed, that it genetically close to West-african strains, belong to II clades and were descended from a common ancestor. Many cases of disease in humans in the current outbreak have been traced to sexual transmission especially among men, who identify ourselves as gay or bisexual. The basis method for identification of agent in present time is PCR-RT targeting on the tumor necrosis factor (TNF) receptor gene. Usually monkeypox of human is mild, self-limiting disease. The symptoms of monkeypox are varied and non-specific. One of the most frequently observed clinical symptoms is lymphadenopathy. Most patients recover during some weeks. However, specific antiviral treatment – tecovirimat (S-246) and brincidofovir (CMX-001) – may be used for seriously ill or immunocompromised individuals. For prophylactic disease in present time are use vaccines JYNNEOSTM, ACAM2000R and Aventis Pasteur (APSV). Conclusion. General vaccination against monkeypox don't develop accordingly to modern recommendations WHO. Ring vaccination is recommended to conduct for suppression of spread virus in nidus of infection among population. Timely international coordination is needed to prevent the global spread of a disease with epidemic potential.

Introduction. When a new disease occurs, one of the most affordable remedies is drugs containing specific antibodies to this infectious agent. The use of such drugs is aimed at reducing the amount of the pathogen in the macroorganism and the associated reduction in the severity of the symptoms of the disease or recovery. The purpose of this review is to analyze the experience of using immunoglobulins and monoclonal antibodies in the treatment of COVID-19 patients during the pandemic. Results and conclusion. The two main groups of medical protective agents that block the penetration of the SARS-CoV-2 virus into permissive cells are drugs obtained from blood plasma of convalescents (immunoglobulin) and human monoclonal antibodies. The first group of drugs in the treatment of COVID-19 includes blood plasma of convalescents, which can be successfully used for emergency prevention. The main disadvantage of using blood plasma convalescents is the difficulty of standardization due to the different content of specific antibodies in donors. Another disadvantage is the undesirable side effects in recipients that occur after plasma administration. An alternative approach to COVID-19 therapy is the use of humanized and genetically engineered human monoclonal antibodies against certain epitopes of the SARS-CoV-2 virus. For example, monoclonal antibodies against receptor-binding domain of the S-protein, which prevents the virus from entering permissive cells and interrupts the development of infection. The advantages of these drugs are their safety, high specific activity, and the possibility of standardization. However, the complexity of their production and high cost make them inaccessible for mass use in practical medicine.

Catastrophic pandemic of the particularly dangerous coronavirus SARS-CoV-2 in 2020–2022 and the unexpected spread of the monkeypox pathogen from Africa in 2022, demonstrate the need for an adequate response to biological threats that have exotic infections as their source, overcome the interspecies barrier between animals and humans and have high rates of virulence and contagiousness in relation to the latter. The purpose of the article is to create a technology for constructing means for the express indication of new especially dangerous and exotic infections, which makes it possible to quickly develop a gene diagnostic tool, evaluate its characteristics and launch large-scale production. Materials and methods. The authors used technologies for constructing means for express indication of new especially dangerous and exotic infections based on real-time polymerase chain reaction (RT-PCR-RT-Flu/ Coronavirus) methods, suitable for multiplex identification of coronavirus RNA. The discussion of the results. The developed technology for constructing means for express indication of new especially dangerous and exotic infections was successfully tested at the laboratory base of the FSBЕ «48 Central Research Institute» of the Ministry of Defense of the Russian Federation using the example of designing a «Set of reagents for detecting the RNA of coronaviruses SARS-CoV, MERS-CoV, SARS-CoV-2 and virus influenza A by real-time polymerase chain reaction (RT-PCR-RT-Flu/Coronavirus)», suitable for multiplex identification of coronavirus RNA. Conclusion. As a result of the research carried out to evaluate the equipment available at the laboratory base of the FSBЕ «48 Central Research Institute» of the Ministry of Defense of the Russian Federation, the adaptation and implementation of key production processes, the development and production of express-indication reagents, as well as testing the technology for constructing express-indication means for new especially dangerous and exotic infections, using the example of designing a set of RT-PCR-RV-Flu/Coronavirus reagents, a gene diagnostic platform was created for the development of reagents for the express indication of new especially dangerous and exotic infections.

The transmission of pathogens from animals to humans is the cause of the appearance of the majority of newly emerging diseases. The purpose of this review is to assess the danger of zoonotic pathogens of dangerous and especially dangerous viral infectious diseases as potential agents of pandemics. Materials and methods. The paper presents an analysis of data published in domestic and English-language scientific publications, as well as posted on the Internet. The research method is analytical. The discussion of the results. At least 70 % of all emerging diseases have a zoonotic reservoir. The exponential growth of human activity in previously undeveloped territories determines the increasing influence of zoonotic pathogens. The infection of people with zoonotic pathogens occurs in direct and indirect contact with infected animals and surfaces contaminated with their secretions, transmissible transmission through arthropod bites, food transport through the consumption of contaminated food and drinking water. Two different transmission models have been established among zoonoses from wild animals to man. One of these models assumes, that human infection is a random event with a low probability, in the future, the pathogen is transmitted from person to person. In the second model, direct or vector-mediated pathogen transfer from animal to human is a link in the natural cycle of the pathogen. The risk of transmission of the virus from the zoonotic reservoir to humans is the highest in animal species adapted to human habitats. Conclusions. The highest level of danger as a source of zoonotic diseases represent primates, ungulates, carnivores and especially bats, which are natural reservoirs for a number of dangerous and especially dangerous viral diseases. Representatives of families Poxviridae, Ortomyxoviridae and Coronaviridae have already been caused pandemics, which caused enormous damage to all spheres of human activity. These pathogens can be considered as the most likely agents of future pandemics.

The analysis of existing information about invasion of COVID-19 in Russia shows that that one of leading reason of existing of new rises of covid-19 morbidity is distribution of new genovariants of SARS-CoV-2 virus. The omicron genovariant of SARS-CoV-2 virus was a dominant agent of fifth and subsequent rises of COVID-19 morbidity in Russia. The aim of this work – the estimation of sublines of omicron genovariant of SARS-CoV-2 virus as potential dominant agents of new rises of COVID-19 morbidity in Russia. The source base of the study. Data published in Russian and English-language scientific publications available via the Internet (RSCI, PubMed, Google Scholar). The research method is analytical. Results. The basic properties of omicron genovariant of SARS-CoV-2 virus, epidemical characteristics of the rises of COVID-19 morbidity in Russia, caused by new sublines of omicron variant, estimation ofsublines of omicron genovariant as potential dominant agent of new rises of COVID-19 morbidity in Russia are viewed. It is shown that basic direction of SARS-CoV-2 virus evolution is existing of sublines of omicron genovariant, which are characterized by increased transmissivity but with less severity of the disease caused compared to previously circulated variants of COVID-19agent. The main distinguishing feature of the new subvariants («Kraken», «Czerber», «Centaur», «Arktur», «Pirola») are multiple amino acid exchanges in structural glycoprotein S. The maximum level of variability of this structural protein compared to the original variant of SARS-CoV-2 virus is marked for Pirola subvariant. Onle Kraken subvariant was dominant agent of rise of COVID-19 morbidity in Russia. Conclusion. New rises of COVID-19 morbidity in Russia will not be connected with existing of new subvariants of omicron genovariant, but only with season factor.

Determining the oxidation potential (OP) of lithium-ion battery (LIB) electrolytes using theoretical methods will significantly speed up and simplify the process of creating a new generation high-voltage battery. The algorithm for calculating OP should be not only accurate but also fast. Our work proposes theoretical principles for evaluating the OP of LIB electrolytes by considering LiDFOB solutions with different salt concentrations in EC/DMC solvent mixtures. The advantage of the new algorithm compared to previous versions of the theoretical determination of the oxidation potential of electrolyte solutions used in lithium-ion batteries for calculations of statistically significant complexes, the structure of which was determined by the molecular dynamics method. This approach significantly reduces the number of atomic–molecular systems whose geometric parameters need to be optimized using quantum chemical methods. Due to this, it is possible to increase the speed of calculations and reduce the power requirements of the computer performing the calculations. The theoretical calculations included a set of approaches based on the methods of classical molecular mechanics and quantum chemistry. To select statistically significant complexes that can make a significant contribution to the stability of the electrochemical system, a thorough analysis of molecular dynamics simulation trajectories was performed. Their geometric parameters (including oxidized forms) were optimized by QM methods. As a result, oxidation potentials were assessed, and their dependence on salt concentration was described. Here, we once again emphasize that it is difficult to obtain, by calculation methods, the absolute OP values that would be equal (or close) to the OP values estimated by experimental methods. Nevertheless, a trend can be identified. The results of theoretical calculations are in full agreement with the experimental ones.

After the abolition of the mandatory smallpox vaccination, the humanity lost the immunity not only to smallpox, but also to infections caused by pathogens of this family (Orthopoxvirus): monkeypox, cowpox, buffalo pox, camelpox. Since the camelpox and African gerbil viruses are the closest to the variola virus (genomic homology is 97%) in phylogenetic and genetic terms, it cannot be ruled out that a mutation in a small fragment of the genome of one of these viruses will lead to the replacement of a relatively safe virus with an epidemically dangerous pathogen. The purpose of is article is to summarize materials on the study of camelpox virus. The sources for this research is scientific articles and other English-language literature available via the Internet. The research method is an analysis of scientific sources on camelpox from the general to the specific. The authors considered the epizootic danger of the virus, its virulence for humans, phylogenetic relationship with other orthopoxviruses, means of specific prevention and treatment of camel pox in camels. The discussion and the results. The causative agent of camelpox causes a nodular-pastular rash on the skin and mucous membranes in Camelus dromedaries and Camelus bactrianus. The disease is contagious, and its epizootics lead to significant economic damage. From December 2008 to May 2009, several laboratory-confirmed cases of camelpox in humans were reported in India, Somalia and eastern Sudan. Nowadays for the identification of the camelpox virus, a RT-PCR test system with primers for the C18L gene is usually offered, which detects only this virus. The established host range of the virus is limited to one animal - the camel. To treat sick camels, chemotherapy drugs are used: cidofovir and tocoverimate (ST-246). For immunoprophylaxis, live and inactivated vaccines are used. The conclusion. Camelpox virus poses a risk to humans in regions where people raise camels and are in close contact with them. The immunodeficient populations of people may serve as an additional «window» for the penetration of this virus into human society. The genetic variability of the virus and the plasticity of its genome make it possible to obtain virus strains with altered properties. Synthetic biology methods create a risk, through small substitutions in the genome of the virus, of turning it into an epidemic danger for humans. Constant monitoring of this disease is necessary, since there is a danger of the transmission of camelpox from Kazakhstan to areas bordering the Russian Federation.

The aim of this review was to investigate the use of the vaccines based on vaccinia virus, MVA stain, and adenovirus vectors for the prevention of Ebola virus disease. The recombinant MVA strains expressing antigen determinants of Filoviridae family representatives were assessed as possible candidates for vaccine preparations. Application of this virus as a vaccine vector is conditioned by the absence of herd immunity to smallpox and its safety for healthy adult volunteers, children, adolescents, individuals suffering from tuberculosis, persons aged 56–80 years, people with diagnosed atopic dermatitis, AIDS. Furthermore, immunization with the vaccine on the basis of vaccinia virus, MVA strain, does not cause complications associated with cardiovascular diseases. Preclinical trials on immunogenicity and protective efficiency were carried out on immune-competent and immune-compromised mice; guinea pigs adapted to Ebola virus; rhesus macaques and cynomolgus monkeys. Presented are the results of experiments on the creation of vaccines expressing either only viral glycoprotein or viral glycoprotein and structural protein Vp40. Given that Ebola fever and other filovirus infection outbreaks are hard to predict, multivalent vaccines that would be able to provide protection against all filovirus species were designed. Clinical trials on simultaneous use of the vaccines based on recombinant adenovirus vectors and MVA strain showed more pronounced safety of vaccines on the basis of recombinant MVA strain. Studies of humoral and T-cell immune responses have revealed that this vector is more suitable for booster vaccination in case of heterologous prime/booster immunization scheme. Vaccination regimens for forming strong durable immune responses have been analyzed. Epidemiological modeling provided evidence that preventive immunization leading to long-term immunity in healthy population in areas of high epidemic risk will be of greater benefit in terms of controlling future outbreaks compared to ring immunization that was effective during smallpox eradication campaign. Increased immunity level, induced by prime/booster vaccination, persisting for a long period of time, will have an advantage over accelerated ring immunization; when the duration of protection is more significant than the speed it is formed at.

The article presents an analysis of studies assessing the effectiveness of new nonspecific medications against hemorrhagic fevers caused by arenaviruses. The possible targets for nonspecific medications, classes of researched antiviral preparations, methods of preclinical investigation of antiviral preparations in vitro and on laboratory animals, as well as prospects for their use in healthcare at present are considered. It has been shown that the level of development of nonspecific medications against hemorrhagic fevers caused by arenaviruses is significantly inferior to those against filovirus infections. Favipiravir should currently be considered as the most effective nonspecific medication against hemorrhagic fevers caused by arenaviruses.

Abstract Materials keeping thickness in atomic scale but extending primarily in lateral dimensions offer properties attractive for many emerging applications. However, compared to crystalline counterparts, synthesis of atomically thin films in the highly disordered amorphous form, which avoids nonuniformity and defects associated with grain boundaries, is challenging due to their metastable nature. Here we present a scalable and solution-based strategy to prepare large-area, freestanding quasi-2D amorphous carbon nanomembranes with predominant sp2 bonding and thickness down to 1–2 atomic layers, from coal-derived carbon dots as precursors. These atomically thin amorphous carbon films are mechanically strong with modulus of 400 ± 100 GPa and demonstrate robust dielectric properties with high dielectric strength above 20 MV cm−1 and low leakage current density below 10−4 A cm−2 through a scaled thickness of three-atomic layers. They can be implemented as solution-deposited ultrathin gate dielectrics in transistors or ion-transport media in memristors, enabling exceptional device performance and spatiotemporal uniformity.

The research relevance is determined by an insufficient study of morphological changes in the mesentery of cats with infectious peritonitis, even though their understanding is necessary to explain the mechanism of development of the main symptom of the disease – the effusion of fluid into the abdominal cavity. The research aims to establish gross and microscopic changes in the mesentery of the small intestine of cats with infectious peritonitis. The research employs gross and histological examination of the mesentery of the small intestine of cats at the infectious peritonitis. Slides of the mesentery were stained with haematoxylin and eosin. At dry and mixed forms of infectious peritonitis, gross and microscopic changes in the mesentery of the small intestine of cats are similar. In the mesentery grossly, small white spots were found, which protruded above the general surface and had a homogeneous appearance on the section. Microscopic changes in the mesentery of the small intestine of cats with dry and mixed forms of infectious peritonitis were also similar. When conducting histological studies, it was established that the mesothelium on the surface of the mesentery was necrotized or absent. The submesothelial layer of collagen fibres was necrotized or contained partially lysed and fragmented fibres. The loose fibrous connective tissue of the mesentery was swollen, necrotized in places, and infiltrated by lymphocytes, monocytes, and macrophages. Eosinophilic inclusion bodies were detected in the cytoplasm of some monocytes and macrophages. Foci of adipose tissue in the mesentery of the small intestine were infiltrated by lymphocytes and monocytes. Necrosis and destruction of their walls were found in blood vessels and destruction of endothelial cells in lymphatic vessels. Perivascular lymphoid nodules were markedly enlarged due to their swelling and an increase in the number of cells in them. In perivascular lymphoid nodules, expansion of lymphatic vessels and destruction of part of their endothelium cells were also established. Some of the lymphatic vessels of the mesentery were expanded and filled with lymph, which contained a significant number of lymphocytes, monocytes, and single neutrophils. The materials presented in the article are of practical value for anatomists, histologists and pathomorphologists, as well as for scientists who study the pathogenesis of infectious peritonitis in cats

Relevance. Ebola virus disease (EVD) is an acute infectious disease with an extremely high case fatality rate reaching up to 90%. EVD has become widely known since 20142016, when outbreak in West Africa occurred and led to epidemic, which caused travel-related cases on the territory of other continents. There are two vaccines against EVD, prequalified by WHO for emergency use, as well as a number of vaccines, approved by local regulators in certain countries. However, even with the availability of effective vaccines, the lack of data on immune correlates of protection and duration of protective immune response in humans and primates is limiting factor for effectively preventing the spread of EVD outbreaks. Aims. This review highlights experience of use of EVD vaccines during outbreaks in endemic areas, summarizes data on vaccine immunogenicity in clinical trials, and discusses perspectives for further development and use of effective EVD vaccines.

At the beginning of 2020, humanity faced the pandemic of a novel coronavirus infection – COVID-19. The disease has become one of the most contagious for the entire history of mankind. Among medical means of protection, which can be used for prophylactics and treatment of COVID-19, non-specific medical medical protection means play an important role. The aim of this work is to analyze and evaluate the effectiveness of non-specific medical protection means against COVID-19. These medications are divided in two groups in accordance with the targets of their actions. The medications of the first group either block the virus from entering the cell, or inhibit the enzymes involved in viral RNA replication. The other group of medications affects the immune system of a macroorganism, which plays a crucial role in infection resistance, or blocks inflammatory processes in the lungs. Favipiravir is an example of a broad-spectrum antiviral drug with an established activity against SARS-CoV-2 in particular. During the development of new non-specific medical protection means against COVID-19, a comprehensive validation in representative randomized clinical trials is an important condition for their implementation in medical practice.

Scientific relevance. The immunoglobulin A (IgA) impurity content in parenteral human immunoglobulins should be determined in accordance with the State Pharmacopoeia of the Russian Federation by kinetic nephelometry, radial immunodiffusion, or enzyme immunoassay (ELISA) with a reference standard. The International Standard (IS) for the content of IgA is certified using gravimetry and radial immunodiffusion. However, neither of the existing standards for the content of IgA in human immunoglobulins is currently certified using all three compendial methods. This prevents analysts from comparing test results obtained by different methods and may lead to an underestimation of the IgA content in human immunoglobulins.Aim. This study aimed to determine the procedure for the development, certification, and use of a pharmacopoeial reference standard (RS) for the content of IgA in human immunoglobulins.Materials and methods. The authors studied candidate RSs for the IgA content derived from human plasma for fractionation. The IgA content determination involved kinetic nephelometry, radial immunodiffusion, and ELISA, as well as commercial test kits and the IS. The authors quantified the IgA impurity in samples of commercial human immunoglobulins from various manufacturers. The data analysis involved descriptive statistics and variance analysis using Microsoft Excel and Statistica 10.Results. The authors established a pharmacopoeial standard with a certified IgA content of 1.98 mg/mL (expanded uncertainty, 0.44 mg/mL; coverage coefficient, k=2; confidence level, 95%) for IgA impurity quantification in human immunoglobulins by radial immunodiffusion and ELISA and that of 1.31–2.64 mg/mL (expanded uncertainty, 0.67 mg/mL; coverage ratio, k=3; confidence level, 99%) for intralaboratory quality control of IgA impurity quantification by kinetic nephelometry, radial immunodiffusion, and ELISA.Conclusions. The pharmacopoeial standard developed in the study has been included in the register of standards of the State Pharmacopoeia of the Russian Federation as the Reference Standard for the Content of Immunoglobulin Class A (IgA) (Registry No. 3.1.00454). The pharmacopoeial standard is intended for the standardisation of analytical methods for the-determination of the IgA impurity content in parenteral human immunoglobulins.

This review is dedicated to the peculiarities of pathogenesis of the experimental Bolivian hemorrhagic fever (BHF) - the disease, caused by Machupo virus (Arenaviridae family). The authors come to the conclusion that for carrying out preclinical researches of the medical means of protection (MMP) in vivo on small laboratory animals it is expedient to use guinea pigs, infected with a strain of Chicava or with a variant of Carvallo strain, adapted for these animals. The use of guinea pigs as small laboratory animals when studying pathogenesis of the disease caused by Machupo virus allows to carry out statistically reliable definition of quantitative indices of an experimental infection and to select medicines for the final stage of preclinical assessment. As arenaviruses block the process of formation of interferon (IFN) in the infected organism, mice, defective by IFN formation, are the perspective animal models for the study of BHF pathogenesis and may be used for the study of attenuated variants of Machupo virus. The Javanese macaques (Macaca fascicularis) are the laboratory animals, modeling the pathogenetic manifestations of BHF in humans. They can be used when carrying out the final stages of preclinical assessment of means of medical protection.

The article is dedicated to the review of some hazardous and extremely hazardous emergent viral infections of the beginning of the XXI century – severe acute respiratory syndrome (SARS), Middle­East respiratory syndrome (MERS), Lujo hemorrhagic fever (LHF) and severe fever with thrombocytopenia syndrome (SFTS). Special attention is paid to the time of reveal and identification of infectious agents, their taxonomic belonging, genome organization, possible ways of the appearance of strains, virulent for human beings, to endemic regions, probable ways of infection, reservoirs and transmitters of infection, morbidity and mortality. These infections should be of particular concern because of the severity of illnesses, caused by the above mentioned viruses, the absence of characteristic clinical signs that makes diagnostics more difficult, especially in non­endemic areas, the absence of means of specific prophylaxis and treatment and the difficulties in their identification. The analyze of this emergent viral infections reveals their potential threat for the Armed Forces and population of the Russian Federation in case of accidental or intentional delivery of causative agents of these diseases to the Russian territory.

The purpose of the work is to analyze the distribution, natural reservoirs and potential epidemic hazard of new members of the Filoviridae family – Bombali viruses (genus Ebolavirus), Lloviu (genus Cuevavirus), Mengla (genus Dianlovirus), Xylang (genus Striavirus), and Hungjiao (genus Thamnovirus). New filoviruses were detected in Africa (Bombali virus), Europe (Llovi virus) and in Southeast Asia (Mengla, Xylang and Hungjiao viruses). Bats are a natural reservoir for all known filoviruses. This fact is confirmed by the information about the detection of genomic RNA and virus-specific antibodies in them. The isolation of the genomic RNA of filoviruses from bats with the subsequent sequencing and phylogenetic analysis made it possible to identify the Bombali, Lloviu, Mengla, Xylang and Hungjiao viruses as new representatives of the Filoviridae family and to establish their position on the phylogenetic tree of the Filoviridae family. Despite the current lack of information about the isolation of biologically active virus from bats, as well as in spite of lack of established connection between new filoviruses and human diseases, the information that newly identified filoviruses use the same receptors (Neumann-Peak protein) to enter sensitive cells, as the Ebola and Marburg viruses, that are pathogenic for humans, the possible pathogenetic potential of new filoviruses poses a great threat to people living in the territories, inhabited by bats. The possibility of the emergence of new emergent filovirus infections on the territory of Russia necessitates an in-depth study of bats as a natural reservoir of filoviruses in nature.

The aim of the work was to determine the effective ultraviolet (UV) doses required for the disinfection of surfaces contaminated with the SARS-CoV-2 coronavirus using a low-pressure mercury lamp. Materials and methods. To carry out prompt disinfection of surfaces, a specially designed source of UV radiation with a power of 7.5 W at a wavelength of 254 nm in the form of a portable flashlight was employed, which has a high efficiency of UV radiation output and the possibility of long-term autonomous operation from a compact battery. In the studies, a suspension culture of the SARS-CoV-2 coronavirus with biological activity of 5.3∙106 PFU/ml was used. The objects of testing were plastic Petri dishes (disposable) and office paper (grade C, density 80 g/m2 ). Results and discussion. Doses of UV radiation that provide disinfection of surfaces contaminated with the COVID-19 pathogen with an efficiency of 99.0 % (paper) to 99.95 % (plastic) have been determined. The results obtained make it possible to recommend a portable UV irradiator for use in the practice of preventive measures to combat the spread of the disease caused by the SARS-CoV-2 coronavirus.

Reverse transcription-real-time polymerase chain reaction (RT-PCR) is currently the leading laboratory diagnostic tool for COVID-19. With the help of RT-PCR-RT, diagnostics is carried out at the early stages of the development of the disease. The studied clinical samples, as a rule, are swabs from the pharynx and nasopharynx. The aim of the work is to identify and analyze the factors that contribute to false negative results when diagnosing COVID-19 by RT-PCR-RT. It is shown in the article, that the analytical sensitivity of the real-time RT-PCR method is not the main factor in assessing the possibility of obtaining false negative results. The paper considers the effect of drinking hot drinks (tea, coffee), alcohol and smoking (immediately before sampling) on the results of the analysis of swabs from the pharynx and nasopharynx by RT-PCR RT. It was found that the intake of hot drinks before sampling (the probability of obtaining a false negative result is at least 80%) influences most of all on the possibility of obtaining a false negative result in RT-PCR-RT in swabs from the pharynx. The use of small doses of alcohol (0.25–0.33 g of ethanol per 1 kg of body weight) has a lesser effect. Smoking immediately prior to sample collection does not lead to a false negative result in real-time RT-PCR. None of the considered influences affects the possibility of obtaining false negative results in the analysis of swabs from the nasopharynx. Recommendations were made on the need for simultaneous examination of both throat swabs and nasopharyngeal swabs in the ongoing diagnosis of COVID-19.

During the COVID-19 pandemic the experts noted the emergence and periodic change of the dominant variants of the coronavirus (SARS-CoV-2) that caused the disease. The line B.1.1529, the omicron variant according to the WHO classification, became dominant in the fifth wave of the COVID-19 pandemic. The aim of the work is to analyze the properties of B.1.1529 (omicron) viruses that ensure its ability to cause disease in vaccinated or previously recovered from COVID-19. The fifth wave is characterized by the parallel distribution of the delta and omicron variants, with the domination of the latter. The omicron variant arose as a result of multiple passages of SARS-CoV-2 through the organisms of immunocompromised patients. If the delta variant is the most virulent for humans, the omicron variant is certainly the most infectious - the value of the basic reproductive number (R0) for it is ≈ 10.0, for the delta variant ≈ 6, 0. A person infected with the omicron variant is capable of transmitting the SARS-CoV-2 virus within a day. This is caused by a combination of N501Y and Q498R mutations in the omicron variant, which increase the affinity of the receptor-binding domain of the S1 subunit of the viral S protein for the ACE-2 receptor in the human lung. Mutations H655Y and N679K are located near the furin cleavage site, which in turn promotes accelerated cleavage of the S-protein and increases the level of infectiousness of the pathogen. The omicron variant is significantly superior to the delta variant in terms of ability to overcome the immunity caused by vaccination. The spread of the disease was not stopped by the fact that the number of people who completed the full course of vaccination at the beginning of the fifth wave in Russia reached 64%.Therefore, the achieved level of vaccination cannot be considered sufficient to stop the spread of this variant of the virus. It is shown in the article, that this indicator should be at least 80% to prevent the spread of the disease, and only if vaccination is carried out in a short time. However, it is possible that the mutational potential of the SARS-CoV-2 virus has not yet been exhausted, and the pandemic on the omicron variant will not end.

Among the epidemic variants of the SARS-CoV-2 virus the main attention is currently attracted by the delta variant (B.1.617), first identified in India in the end of 2020. Since the appearance of the delta variant, the morbidity rate of COVID-19 in India has increased 20-fold. The overflow of the delta variant of the SARS-CoV-2 virus outside of India is one of the factors in the emergence of the third wave of the COVID-19 pandemic. As of August 24, 2021 the delta variant of SARS-CoV-2 virus has been identified in 193 countries. The purpose of this work is to analyze the delta variant of SARSCoV-2 virus and the features of the disease caused by it. The main features of the delta variant are: a set of mutations affecting a significant functional area of S-protein; a transfer rate from person to person; a reduced incubation period of caused disease. In Russia, the delta variant of SARS-CoV-2 virus appears no earlier than the end of April – beginning of May, 2021. The spread of the delta variant as the dominant one is associated with the emergence in early June 2021 of the third, and in mid-September – the fourth wave of the COVID-19 epidemic in Russia. The epidemiological data for Russia show a sharp increase in the number of new cases of the disease, with a simultaneous increase in the number of hospitalizations and deaths of the disease. The necessary measures to combat the epidemic are: first of all, accelerating the pace of vaccination, as well as the set of administrative measures, including limiting mass events, strict observance of the mask regime and social distance in public places.