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Strategies to Prevent SARS-CoV-2-Mediated Eosinophilic Disease in Association with COVID-19 Vaccination and Infection
No full textA vaccine to protect against COVID-19 is urgently needed. Such a vaccine should efficiently induce high-affinity neutralizing antibodies which neutralize SARS-CoV-2, the cause of COVID-19. However, there is a concern regarding both vaccine-induced eosinophilic lung disease and eosinophil-associated Th2 immunopotentiation following infection after vaccination. Here, we review the anticipated characteristics of a COVID-19 vaccine to avoid vaccine-associated eosinophil immunopathology. © 202
Emergency services of viral RNAs: Repair and remodeling
No full textReproduction of RNA viruses is typically error-prone due to the infidelity of their replicative machinery and the usual lack of proofreading mechanisms. The error rates may be close to those that kill the virus. Consequently, populations of RNA viruses are represented by heterogeneous sets of genomes with various levels of fitness. This is especially consequential when viruses encounter various bottlenecks and new infections are initiated by a single or few deviating genomes. Nevertheless, RNA viruses are able to maintain their identity by conservation of major functional elements. This conservatism stems from genetic robustness or mutational tolerance, which is largely due to the functional degeneracy of many protein and RNA elements as well as to negative selection. Another relevant mechanism is the capacity to restore fitness after genetic damages, also based on replicative infidelity. Conversely, error-prone replication is a major tool that ensures viral evolvability. The potential for changes in debilitated genomes is much higher in small populations, because in the absence of stronger competitors low-fit genomes have a choice of various trajectories to wander along fitness landscapes. Thus, low-fit populations are inherently unstable, and it may be said that to run ahead it is useful to stumble. In this report, focusing on picornaviruses and also considering data from other RNA viruses, we review the biological relevance and mechanisms of various alterations of viral RNA genomes as well as pathways and mechanisms of rehabilitation after loss of fitness. The relationships among mutational robustness, resilience, and evolvability of viral RNA genomes are discussed. © 2018 American Society for Microbiology. All Rights Reserved
A Novel Antiviral Strategy against MERS-CoV and HCoV-229E Using Binase to Target Viral Genome Replication
No full textRNA viruses cause most of the dangerous communicable diseases. Due to their high mutation rates, RNA viruses quickly evade selective pressures and can adapt to a new host. Therefore, new antiviral approaches are urgently needed, which target more than one specific virus variant and which would optimally prevent development of viral resistance. Among the family of coronaviruses (CoV), several human pathogenic strains (HCoV) are known to cause respiratory diseases and are implied in enteric diseases. While most strains contribute to common cold-like illnesses, others lead to severe infections. One of these viruses is the newly emerged (2012), highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) of zoonotic origin. MERS-CoV causes a severe respiratory infection with a high mortality rate of 35 %. There is no specific treatment or infection prevention available. Here, we show that the bacterial ribonuclease Binase is able to inhibit the replication of MERS-CoV and of the low-pathogenic human coronavirus 229E (HCoV-229E) in cell culture. We demonstrate that at non-toxic concentrations, Binase decreased the titers of MERS-CoV and HCoV-229E. On a molecular level, Binase treatment reduced (i) the viral subgenomic RNAs and (ii) the viral nucleocapsidprotein (N) and non-structural protein 13 (nsp13) accumulation. Furthermore, we show that the quantity of the replication/transcription complexes within the infected cells is diminished. Thus, the data obtained might allow further development of new anti-coronaviral approaches affecting viral replication, independent of the specific virus strain. © 2016, Springer Science+Business Media New York
H2N2 live attenuated influenza vaccine is safe and immunogenic for healthy adult volunteers
No full textH2N2 influenza viruses have not circulated in the human population since 1968, but they are still being regularly detected in the animal reservoir, suggesting their high pandemic potential. To prepare for a possible H2N2 pandemic, a number of H2N2 vaccine candidates have been generated and tested in preclinical and clinical studies. Here we describe the results of a randomized, double-blind placebo-controlled phase 1 clinical trial of an H2N2 live attenuated influenza vaccine (LAIV) candidate prepared from a human influenza virus isolated in 1966. The vaccine candidate was safe and well-tolerated by healthy adults, and did not cause serious adverse events or an increased rate of moderate or severe reactogenicities. The H2N2 vaccine virus was infectious for Humans. It was shed by 78.6% and 74.1% volunteers after the first and second dose, respectively, most probably due to the human origin of the virus. Importantly, no vaccine virus transmission to unvaccinated subjects was detected during the study. We employed multiple immunological tests to ensure the adequate assessment of the H2N2 pandemic LAIV candidate and demonstrated that the majority (92.6%) of the vaccinated subjects responded to the H2N2 LAIV in one or more immunological tests, including 85.2% of subjects with antibody responses and 55.6% volunteers with cell-mediated immune responses. In addition, we observed strong correlation between the H2N2 LAIV virus replication in the upper respiratory tract and the development of antibody responses. © 2015 Taylor & Francis Group, LLC
Micro-and meso-level influences on obesity in the former Soviet Union: A multi-level analysis
No full textBackground: Limited evidence exists on obesity in the former Soviet Union (fSU), particularly its micro- and meso-level determinants. The objectives of this study were to determine age- and gender-adjusted prevalence of self-reported overweight and obesity in nine fSU countries; explore the relationship between individual and household (micro-level) factors and obesity; and explore the relationship between features of nutritional and physical environments (meso-level) and obesity. Methods: Data were collected from 18 000 adults using household surveys and from 333 communities using community profiles in Azerbaijan, Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia and Ukraine in 2010. Individual- and community-level determinants of self-reported obesity (body mass index 30 kg/m2) were analysed using multi-level random intercept logistic regression models. Results: A total of 13% of the males and 18% of the females were categorized as obese. Factors associated with obesity in males were older age, increasing educational achievement, declining self-reported health, alcohol consumption and automobile ownership. Males who were current smokers, not married and perceived physical activity to be important were less likely to be obese. For females, obesity was associated with older age, completion of secondary-level education, declining self-reported health and average household financial situation. Unmarried women were less likely to be obese. Multi-level analysis indicated that individuals living in communities with higher presence of garbage were more likely to be obese. Conclusions: This is the first study to examine both micro- and meso-level influences on obesity in fSU using multi-level analysis. Findings indicate a similar obesity risk profile to countries in Western Europe and North America. © 2012 Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved
Efficient discrimination within a Corynebacterium diphtheriae epidemic clonal group by a novel macroarray-based method
No full textA large diphtheria epidemic in the 1990s in Russia and neighboring countries was caused by a clonal group of closely related Corynebacterium diphtheriae strains (ribotypes Sankt-Peterburg and Rossija). In the recently published complete genome sequence of C. diphtheriae strain NCTC13129, representative of the epidemic clone (A. M. Cerdeño-Tarraga et al., Nucleic Acids Res. 31:6516-6523, 2003), we identified in silico two direct repeat (DR) loci 39 kb downstream and 180 kb upstream of the oriC region, consisting of minisatellite (27- to 36-bp) alternating DRs and variable spacers. We designated these loci DRA and DRB, respectively. A reverse-hybridization macroarray-based method has been developed to study polymorphism (the presence or absence of 21 different spacers) in the larger DRB locus. We name it spoligotyping (spacer oligonucleotide typing), analogously to a similar method of Mycobacterium tuberculosis genotyping. The method was evaluated with 154 clinical strains of the C. diphtheriae epidemic clone from the St. Petersburg area in Russia from 1997 to 2002. By comparison with the international ribotype database (Institut Pasteur, Paris, France), these strains were previously identified as belonging to ribotypes Sankt-Peterburg (n = 79) and Rossija (n = 75). The 154 strains were subdivided into 34 spoligotypes: 14 unique strains and 20 types shared by 2 to 46 strains; the Hunter Gaston discriminatory index (HGDI) was 0.85. DRB locus-based spoligotyping allows fast and efficient discrimination within the C. diphtheriae epidemic clonal group and is applicable to both epidemiological investigations and phylogenetic reconstruction. The results are easy to interpret and can be presented and stored in a user-friendly digital database (Excel file), allowing rapid type determination of new strains. Copyright © 2005, American Society for Microbiology. All Rights Reserved
The surface glycoproteins of H5 influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable properties
No full textIn 1997, 18 confirmed cases of human influenza arising from multiple independent transmissions of H5N1 viruses from infected chickens were reported from Hong Kong. To identify possible phenotypic changes in the hemagglutinin (HA) and neuraminidase (NA) of the H5 viruses during interspecies transfer, we compared the receptor-binding properties and NA activities of the human and chicken H5N1 isolates from Hong Kong and of H5N3 and HSN1 viruses from wild aquatic birds. All H5N1 viruses, including the human isolate bound to Sia2-3Gal-containing receptors but not to Sia2-6Gal- containing receptors. This finding formally demonstrates for the first time that receptor specificity of avian influenza viruses may not restrict initial avian-to-human transmission. The HSN1 chicken viruses differed from H5 viruses of wild aquatic birds by a 19-amino-acid deletion in the stalk of the NA and the presence of a carbohydrate at the globular head of the HA. We found that a deletion in the NA decreased its ability to release the virus from cells, whereas carbohydrate at the HA head decreased the affinity of the virus for cell receptors. Comparison of amino acid sequences from GenBank of the HAs and NAs from different avian species revealed that additional glycosylation of the HA and a shortened NA stalk are characteristic features of the H5 and H7 chicken viruses. This finding indicates that changes in both HA and NA may be required for the adaptation of influenza viruses from wild aquatic birds to domestic chickens and raises the possibility that chickens may be a possible intermediate host in zoonotic transmission
A Novel Strategy for the Development of Vaccines for SARS-CoV-2 (COVID-19) and Other Viruses Using AI and Viral Shell Disorder
No full textA model that predicts levels of coronavirus (CoV) respiratory and fecal-oral transmission potentials based on the shell disorder has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Using primarily the PID of N, SARS-CoV-2 is grouped as having intermediate levels of both respiratory and fecal-oral transmission potentials. Related studies, using similar methodologies, have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and case-fatality rates of 0.5-5% and 10.9%, respectively. The underlying relationship between virulence and respiratory potentials has to do with the viral loads of vital organs and body fluids, respectively. Viruses can spread by respiratory means only if the viral loads in saliva and mucus exceed certain minima. Similarly, a patient is likelier to die when the viral load overwhelms vital organs. Greater disorder in inner shell proteins has been known to play important roles in the rapid replication of viruses by enhancing the efficiency pertaining to protein-protein/DNA/RNA/lipid bindings. This paper suggests a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells (N) of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore, this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its greater contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed. © 2020 American Chemical Society. All rights reserved
The Future of Distance Learning as Perceived by Faculty Members
No full textA questionnaire survey of 33,987 faculty members in April 2020 revealed predominantly negative evaluations of learning effectiveness in the context of distance learning, as compared to in-person instruction, and a rather pessimistic vision of the future of higher education in Russia. This article formulates hypotheses about the reasons of such attitudes among faculty members and provides arguments for possible opinion shifts and alleviation of resistance to technological change. The paramount problem consists in the contradiction between the acceptance of the idea and value of digital innovation and the rejection of such at the level of personal teaching practices. During expert interviews, faculty members were offered alternative scenarios of the future. The data obtained was then used to analyze the attitudes and beliefs behind their resistance and to find out which perceptions of the future correlated with negative and positive evaluations of distance learning
Resilience of a Territory: Concept, Measurement, Governance
No full textAbstract—The paper considers problems of adequate interpretation of the term resilience in relation to the term sustainable development and offers a consistent holistic system of concepts based on the term shock resistance (shokoustoichivost’), which allows to discuss the problems of sustainable development and resilience (without mixing these terms). The directions for creating a methodology for measuring resilience are proposed, based on a study of theoretical and methodological approaches and existing attempts to measure the resilience of cities and regions. The article describes existing Russian examples of measuring the resilience of regions a posteriori (by analyzing the behavior of indicators of socioeconomic development during and after economic and budgetary crises) and a priori (based on the characteristics of industry structure or risk resistance of the economic, social, and governance subsystems of a region). A paradox is noted: in Russia, subsidization of a region and a backward structure of the economy are factors that increase resilience. Ways are shown to embed mechanisms for increasing resilience in the strategic governance system of urban and regional development. It is proposed to introduce resilience auditing into management practice and create a regional (municipal) risk-management system and the position of a risk manager