18 results on '"Pochtovyi AA"'
Search Results
2. Development of novel antimicrobials with engineered endolysin LysECD7-SMAP to combat Gram-negative bacterial infections.
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Vasina DV, Antonova NP, Gushchin VA, Aleshkin AV, Fursov MV, Fursova AD, Gancheva PG, Grigoriev IV, Grinkevich P, Kondratev AV, Kostarnoy AV, Lendel AM, Makarov VV, Nikiforova MA, Pochtovyi AA, Prudnikova T, Remizov TA, Shevlyagina NV, Siniavin AE, Smirnova NS, Terechov AA, Tkachuk AP, Usachev EV, Vorobev AM, Yakimakha VS, Yudin SM, Zackharova AA, Zhukhovitsky VG, Logunov DY, and Gintsburg AL
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- Animals, Mice, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents administration & dosage, Rats, Male, Protein Engineering methods, Gram-Negative Bacterial Infections drug therapy, Endopeptidases pharmacology, Endopeptidases administration & dosage, Mice, Inbred BALB C, Gram-Negative Bacteria drug effects
- Abstract
Background: Among the non-traditional antibacterial agents in development, only a few targets critical Gram-negative bacteria such as carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii or cephalosporin-resistant Enterobacteriaceae. Endolysins and their genetically modified versions meet the World Health Organization criteria for innovation, have a novel mode of antibacterial action, no known bacterial cross-resistance, and are being intensively studied for application against Gram-negative pathogens., Methods: The study presents a multidisciplinary approach, including genetic engineering of LysECD7-SMAP and production of recombinant endolysin, its analysis by crystal structure solution following molecular dynamics simulations and evaluation of antibacterial properties. Two types of antimicrobial dosage forms were formulated, resulting in lyophilized powder for injection and hydroxyethylcellulose gel for topical administration. Their efficacy was estimated in the treatment of sepsis, and pneumonia models in BALB/c mice, diabetes-associated wound infection in the leptin receptor-deficient db/db mice and infected burn wounds in rats., Results: In this work, we investigate the application strategies of the engineered endolysin LysECD7-SMAP and its dosage forms evaluated in preclinical studies. The catalytic domain of the enzyme shares the conserved structure of endopeptidases containing a putative antimicrobial peptide at the C-terminus of polypeptide chain. The activity of endolysins has been demonstrated against a range of pathogens, such as Klebsiella pneumoniae, A. baumannii, P. aeruginosa, Staphylococcus haemolyticus, Achromobacter spp, Burkholderia cepacia complex and Haemophylus influenzae, including those with multidrug resistance. The efficacy of candidate dosage forms has been confirmed in in vivo studies. Some aspects of the interaction of LysECD7-SMAP with cell wall molecular targets are also discussed., Conclusions: Our studies demonstrate the potential of LysECD7-SMAP therapeutics for the systemic or topical treatment of infectious diseases caused by susceptible Gram-negative bacterial species and are critical to proceed LysECD7-SMAP-based antimicrobials trials to advanced stages., (© 2024. The Author(s).)
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- 2024
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3. Major Role of S-Glycoprotein in Providing Immunogenicity and Protective Immunity in mRNA Lipid Nanoparticle Vaccines Based on SARS-CoV-2 Structural Proteins.
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Bykonia EN, Kleymenov DA, Gushchin VA, Siniavin AE, Mazunina EP, Kozlova SR, Zolotar AN, Usachev EV, Kuznetsova NA, Shidlovskaya EV, Pochtovyi AA, Kustova DD, Ivanov IA, Dmitriev SE, Ivanov RA, Logunov DY, and Gintsburg AL
- Abstract
SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed. Based on our recently studied mRNA lipid nanoparticle (mRNA-LNP) platform, we have generated mRNA-LNP encoding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combination in vivo. As a result, all mRNA-LNP vaccine compositions encoding the S and N proteins induced excellent titers of RBD- and N-specific binding antibodies. The T cell responses were mainly specific CD4
+ T cell lymphocytes producing IL-2 and TNF-alpha. mRNA-LNP encoding the M protein did not show a high immunogenicity. High neutralizing activity was detected in the sera of mice vaccinated with mRNA-LNP encoding S protein (alone or in combinations) against closely related strains, but was undetectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to mRNA-N in the vaccine composition enhanced the immunogenicity of mRNA-N and induced a more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancing the immune response to the N protein when they are both encoded in the mRNA-LNP vaccine.- Published
- 2024
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4. In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1.
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Pochtovyi AA, Kustova DD, Siniavin AE, Dolzhikova IV, Shidlovskaya EV, Shpakova OG, Vasilchenko LA, Glavatskaya AA, Kuznetsova NA, Iliukhina AA, Shelkov AY, Grinkevich OM, Komarov AG, Logunov DY, Gushchin VA, and Gintsburg AL
- Abstract
The spread of COVID-19 continues, expressed by periodic wave-like increases in morbidity and mortality. The reason for the periodic increases in morbidity is the emergence and spread of novel genetic variants of SARS-CoV-2. A decrease in the efficacy of monoclonal antibodies (mAbs) has been reported, especially against Omicron subvariants. There have been reports of a decrease in the efficacy of specific antiviral drugs as a result of mutations in the genes of non-structural proteins. This indicates the urgent need for practical healthcare to constantly monitor pathogen variability and its effect on the efficacy of preventive and therapeutic drugs. As part of this study, we report the results of the continuous monitoring of COVID-19 in Moscow using genetic and virological methods. As a result of this monitoring, we determined the dominant genetic variants and identified the variants that are most widespread, not only in Moscow, but also in other countries. A collection of viruses from more than 500 SARS-CoV-2 isolates has been obtained and characterized. The genetic lines XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, representing the greatest concern, were identified among the dominant variants. We studied the in vitro efficacy of mAbs Tixagevimab + Cilgavimab (Evusheld), Sotrovimab, Regdanvimab, Casirivimab + Imdevimab (Ronapreve), and Bebtelovimab, as well as the specific antiviral drugs Remdesivir, Molnupiravir, and Nirmatrelvir, against these genetic lines. At the current stage of the COVID-19 pandemic, the use of mAbs developed against early SARS-CoV-2 variants has little prospect. Specific antiviral drugs retain their activity, but further monitoring is needed to assess the risk of their efficacy being reduced and adjust recommendations for their use.
- Published
- 2023
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5. Revaccination in Age-Risk Groups with Sputnik V Is Immunologically Effective and Depends on the Initial Neutralizing SARS-CoV-2 IgG Antibodies Level.
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Godkov MA, Ogarkova DA, Gushchin VA, Kleymenov DA, Mazunina EP, Bykonia EN, Pochtovyi AA, Shustov VV, Shcheblyakov DV, Komarov AG, Tsibin AN, Zlobin VI, Logunov DY, and Gintsburg AL
- Abstract
Vaccination against COVID-19 has occurred in Russia for more than two years. According to the Russian official clinical guidelines to maintain tense immunity in the conditions of the ongoing COVID-19 pandemic, it is necessary to use booster immunization six months after primary vaccination or a previous COVID-19 contraction. It is especially important to ensure the maintenance of protective immunity in the elderly, who are at risk of severe courses of COVID-19. Meanwhile, the immunological effectiveness of the booster doses has not been sufficiently substantiated. To investigate the immunogenicity of Sputnik V within the recommended revaccination regimen and evaluate the effectiveness of booster doses, we conducted this study on 3983 samples obtained from individuals previously vaccinated with Sputnik V in Moscow. We analyzed the level of antibodies in BAU/mL three times: (i) six months after primary immunization immediately before the booster (RV), (ii) 3 weeks after the introduction of the first component of the booster (RV1), and (iii) 3 weeks after the introduction of the second component of the booster (RV2). Six months after the primary vaccination with Sputnik V, 95.5% of patients maintained a positive level of IgG antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. The degree of increase in the specific virus-neutralizing antibodies level after revaccination increased with a decrease in their initial level just before the booster dose application. In the group of people with the level of antibodies up to 100 BAU/mL six months after the vaccination, a more than eightfold increase (p < 0.001, Wilcoxon criterion with Bonferroni adjustment) in the level of specific antibodies was observed (Me = 8.84 (IQR: 3.63−30.61)). A significant increase in the IgG level after receiving both the first and the second booster doses occurred at the initial titer level up to 300 BAU/ mL (p < 0.001) in those who did not contract COVID-19 in the past and up to 100 BAU/mL (p < 0.001) in those who were previously infected with SARS-CoV-2. A significant increase in the antibody level after the first dose of the booster was noted for people who had up to 500 BAU/mL (p < 0.05), regardless of the previous COVID-19 infection. Thus, revaccination is most effective in individuals with an antibody level below 500 BAU/mL, regardless of the vaccinee age and COVID-19 contraction. For the first time, it has been shown that a single booster dose of the Sputnik vaccine is sufficient to form a protective immunity in most vaccinees regardless of age and preexisting antibody level., Competing Interests: The authors declare no conflict of interest.
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- 2022
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6. Dynamics of SARS-CoV-2 Major Genetic Lineages in Moscow in the Context of Vaccine Prophylaxis.
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Gushchin VA, Pochtovyi AA, Kustova DD, Ogarkova DA, Tarnovetskii IY, Belyaeva ED, Divisenko EV, Vasilchenko LA, Shidlovskaya EV, Kuznetsova NA, Tkachuk AP, Slutskiy EA, Speshilov GI, Komarov AG, Tsibin AN, Zlobin VI, Logunov DY, and Gintsburg AL
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- Humans, SARS-CoV-2 genetics, Pandemics, COVID-19 epidemiology, COVID-19 prevention & control, Vaccines
- Abstract
Findings collected over two and a half years of the COVID-19 pandemic demonstrated that the level immunity resulting from vaccination and infection is insufficient to stop the circulation of new genetic variants. The short-term decline in morbidity was followed by a steady increase. The early identification of new genetic lineages that will require vaccine adaptation in the future is an important research target. In this study, we summarised data on the variability of genetic line composition throughout the COVID-19 pandemic in Moscow, Russia, and evaluated the virological and epidemiological features of dominant variants in the context of selected vaccine prophylaxes. The prevalence of the Omicron variant highlighted the low effectiveness of the existing immune layer in preventing infection, which points to the necessity of optimising the antigens used in vaccines in Moscow. Logistic growth curves showing the rate at which the new variant displaces the previously dominant variants may serve as early indicators for selecting candidates for updated vaccines, along with estimates of efficacy, reduced viral neutralising activity against the new strains, and viral load in previously vaccinated patients.
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- 2022
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7. Estimation of anti-orthopoxvirus immunity in Moscow residents and potential risks of spreading Monkeypox virus.
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Gushchin VA, Ogarkova DA, Dolzhikova IV, Zubkova OV, Grigoriev IV, Pochtovyi AA, Iliukhina AA, Ozharovskaia TA, Kuznetsova NA, Kustova DD, Shelkov AY, Zrelkin DI, Odintsova AS, Grousova DM, Kan VY, Davtyan SA, Siniavin AE, Belyaeva ED, Botikov AG, Bessonova AA, Vasilchenko LA, Vasina DV, Kleymenov DA, Slutskiy EA, Tkachuk AP, Burgasova OA, Loginova SY, Rozhdestvensky EV, Shcheblyakov DV, Tsibin AN, Komarov AG, Zlobin VI, Borisevich SV, Naroditsky BS, Logunov DY, and Gintsburg AL
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- Humans, Adult, Middle Aged, Monkeypox virus, Cross-Sectional Studies, Moscow epidemiology, Vaccinia virus, Antibodies, Neutralizing, Orthopoxvirus, Mpox (monkeypox), Communicable Diseases
- Abstract
WHO has declared the outbreak of monkeypox as a public health emergency of international concern. In less than three months, monkeypox was detected in more than 30 000 people and spread to more than 80 countries around the world. It is believed that the immunity formed to smallpox vaccine can protect from monkeypox infection with high efficiency. The widespread use of Vaccinia virus has not been carried out since the 1980s, which raises the question of the level of residual immunity among the population and the identification of groups requiring priority vaccination. We conducted a cross-sectional serological study of remaining immunity among Moscow residents. To do this, a collection of blood serum samples of age group over 30 years old was formed, an in-house ELISA test system was developed, and a virus neutralization protocol was set up. Serum samples were examined for the presence of IgG antibodies against Vaccinia virus ( n =2908), as well as for the ability to neutralize plaque formation with a Vaccinia virus MNIIVP-10 strain ( n =299). The results indicate the presence of neutralizing antibody titer of 1/20 or more in 33.3 to 53.2% of people older than 45 years. Among people 30-45 years old who probably have not been vaccinated, the proportion with virus neutralizing antibodies ranged from 3.2 to 6.7%. Despite the higher level of antibodies in age group older than 66 years, the proportion of positive samples in this group was slightly lower than in people aged 46-65 years. The results indicate the priority of vaccination in groups younger than 45, and possibly older than 66 years to ensure the protection of the population in case of spread of monkeypox among Moscow residents. The herd immunity level needed to stop the circulation of the virus should be at least 50.25 - 65.28%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gushchin, Ogarkova, Dolzhikova, Zubkova, Grigoriev, Pochtovyi, Iliukhina, Ozharovskaia, Kuznetsova, Kustova, Shelkov, Zrelkin, Odintsova, Grousova, Kan, Davtyan, Siniavin, Belyaeva, Botikov, Bessonova, Vasilchenko, Vasina, Kleymenov, Slutskiy, Tkachuk, Burgasova, Loginova, Rozhdestvensky, Shcheblyakov, Tsibin, Komarov, Zlobin, Borisevich, Naroditsky, Logunov and Gintsburg.)
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- 2022
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8. Sputnik Light and Sputnik V Vaccination Is Effective at Protecting Medical Personnel from COVID-19 during the Period of Delta Variant Dominance.
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Sukhikh GT, Priputnevich TV, Ogarkova DA, Pochtovyi AA, Kustova DD, Zlobin VI, Logunov DY, Gushchin VA, and Gintsburg AL
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Medical personnel are a group of people that often encounter infectious agents, leading to greater risk of contracting infectious diseases. Specific prevention of diseases in this group is a priority. The epidemiological effectiveness of COVID-19 prevention in the group of medical workers due to the emergence of new variants of concern of the SARS-CoV-2 virus has not been studied in sufficient depth. We conducted a study of the effectiveness of vaccine use to protect medical workers at a large medical center for obstetrics and gynecology in Moscow. Sputnik V and Sputnik Light were the main vaccines used for the prevention of COVID-19. The vaccines are based on a variant of the S-protein of the SARS-CoV-2 virus, with adenovirus serotypes 5 and 26 as the vector for delivery. Vaccination of employees occurred during the period in which the Delta variant was spreading. The overall epidemiological effectiveness was 81.7% (73.1-87.6%) during the period in which the Delta variant was dominant. During the period from the beginning of vaccination (26 November 2020) until 8 February 2022, the overall effectiveness was 89.1% (86.9-91.0%). As expected, the highest effectiveness during this period was obtained in the group that received the third and fourth doses-96.5% (75.0-99.5%). The severity of COVID-19 in the vaccinated group was significantly lower than in the unvaccinated group.
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- 2022
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9. Sputnik V Effectiveness against Hospitalization with COVID-19 during Omicron Dominance.
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Shkoda AS, Gushchin VA, Ogarkova DA, Stavitskaya SV, Orlova OE, Kuznetsova NA, Keruntu EN, Pochtovyi AA, Pukhov AV, Kleymenov DA, Krzhanovsky VG, Vasina DV, Shkuratova NV, Shidlovskaya EV, Gorbunov AL, Kustova DD, Mazurina EA, Kozlova SR, Soboleva AV, Grigoriev IV, Pankratyeva LL, Odintsova AS, Belyaeva ED, Bessonova AA, Vasilchenko LA, Lupu IP, Adgamov RR, Tkachuk AP, Tokarskaya EA, Logunov DY, and Gintsburg AL
- Abstract
Mass vaccination campaigns against COVID-19 affected more than 90% of the population in most developed countries. The new epidemiologic wave of COVID-19 has been ongoing since the end of 2021. It is caused by a virus variant B.1.1.529, also known as "Omicron" and its descendants. The effectiveness of major vaccines against Omicron is not known. The purpose of this study is to evaluate the efficacy of the Sputnik V vaccine. The main goal is to assess its protection against hospitalization in the period of Omicron dominance. We conducted our study based on a large clinical center in Moscow (Russia) where 1112 patients were included. We used the case-population method to perform the calculations. The data we obtained indicate that the Omicron variant causes at least 90% of infections in the studied cohort. The effectiveness of protection against hospitalization with COVID-19 in our study was 85.9% (95% CI 83.0-88.0%) for those who received more than one dose. It was 87.6% (95% CI 85.4-89.5%) and 97.0% (95% CI 95.9-97.8%) for those who received more than two or three doses. The effectiveness in cases of more severe forms was higher than for less severe ones. Thus, present study indicates the high protective efficacy of vaccination against hospitalization with COVID-19 in case of Omicron lineage.
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- 2022
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10. Different evolutionary dynamics of hepatitis B virus genotypes A and D, and hepatitis D virus genotypes 1 and 2 in an endemic area of Yakutia, Russia.
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Karlsen AA, Kyuregyan KK, Isaeva OV, Kichatova VS, Asadi Mobarkhan FA, Bezuglova LV, Netesova IG, Manuylov VA, Pochtovyi AA, Gushchin VA, Sleptsova SS, Ignateva ME, and Mikhailov MI
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- Bayes Theorem, Genotype, Hepatitis B virus genetics, Hepatitis Delta Virus genetics, Humans, Phylogeny, Coinfection epidemiology, Hepatitis B, Hepatitis D complications
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Background: The geographic distribution of the hepatitis B virus (HBV) and the hepatitis D virus (HDV) genotypes is uneven. We reconstructed the temporal evolution of HBV and HDV in Yakutia, one of the regions of Russia most affected by HBV and HDV, in an attempt to understand the possible mechanisms that led to unusual for Russia pattern of viral genotypes and to identify current distribution trends., Methods: HBV and HDV genotypes were determined in sera collected in 2018-2019 in Yakutia from randomly selected 140 patients with HBV monoinfection and 59 patients with HBV/HDV. Total 86 HBV and 88 HDV genomic sequences isolated in Yakutia between 1997 and 2019 were subjected to phylodynamic and philogeographic Bayesian analysis using BEAST v1.10.4 software package. Bayesian SkyGrid reconstruction and Birth-Death Skyline analysis were applied to estimate HBV and HDV population dynamics., Results: Currently, HBV-A and HDV-D genotypes are prevalent in Yakutia, in both monoinfected and HDV-coinfected patients. Bayesian analysis has shown that the high prevalence of HBV-A in Yakutia, which is not typical for Russia, initially emerged after the genotype was introduced from Eastern Europe in the fifteenth century (around 600 (95% HPD: 50-715) years ago). The acute hepatitis B epidemics in the 1990s in Yakutia were largely associated with this particular genotype, as indicated by temporal changes in HBV-A population dynamics. HBV-D had a longer history in Yakutia and demonstrated stable population dynamics, indicating ongoing viral circulation despite vaccination. No correlation between HBV and HDV genotypes was observed for coinfected patients in Yakutia (r = - 0.016069332). HDV-2b circulates in Russia in Yakutia only and resulted from a single wave of introduction from Central Asia 135 years ago (95% HPD: 60-350 years), while HDV-1 strains resulted from multiple introductions from Europe, the Middle East, Central Asia, and different parts of Russia starting 180 years ago (95% HPD: 150-210 years) and continuing to the present day. The population dynamics of HDV-1 and HDV-2 show no signs of decline despite 20 years of HBV vaccination. The Birth-Death Skyline analysis showed an increase in the viral population in recent years for both HDV genotypes, indicating ongoing HDV epidemics., Conclusions: Taken together, these data call for strict control of HBV vaccination quality and coverage, and implementation of HBV and HDV screening programs in Yakutia., (© 2022. The Author(s).)
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- 2022
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11. The rise and spread of the SARS-CoV-2 AY.122 lineage in Russia.
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Klink GV, Safina KR, Nabieva E, Shvyrev N, Garushyants S, Alekseeva E, Komissarov AB, Danilenko DM, Pochtovyi AA, Divisenko EV, Vasilchenko LA, Shidlovskaya EV, Kuznetsova NA, Speranskaya AS, Samoilov AE, Neverov AD, Popova AV, Fedonin GG, Akimkin VG, Lioznov D, Gushchin VA, Shchur V, and Bazykin GA
- Abstract
Delta has outcompeted most preexisting variants of SARS-CoV-2, becoming the globally predominant lineage by mid-2021. Its subsequent evolution has led to the emergence of multiple sublineages, most of which are well-mixed between countries. By contrast, here we show that nearly the entire Delta epidemic in Russia has probably descended from a single import event, or from multiple closely timed imports from a single poorly sampled geographic location. Indeed, over 90 per cent of Delta samples in Russia are characterized by the nsp2:K81N + ORF7a:P45L pair of mutations which is rare outside Russia, putting them in the AY.122 sublineage. The AY.122 lineage was frequent in Russia among Delta samples from the start, and has not increased in frequency in other countries where it has been observed, suggesting that its high prevalence in Russia has probably resulted from a random founder effect rather than a transmission advantage. The apartness of the genetic composition of the Delta epidemic in Russia makes Russia somewhat unusual, although not exceptional, among other countries., (© The Author(s) 2022. Published by Oxford University Press.)
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- 2022
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12. Microbiological Characteristics of Some Stations of Moscow Subway.
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Pochtovyi AA, Vasina DV, Verdiev BI, Shchetinin AM, Yuzhakov AG, Ovchinnikov RS, Tkachuk AP, Gushchin VA, and Gintsburg AL
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The subway is one of the most actively used means of transport in the traffic infrastructure of large metropolitan areas. More than seven million passengers use the Moscow subway every day, which promotes the exchange of microorganisms between people and the surrounding subway environment. In this research, a study of the bacterial communities of two Moscow subway stations was conducted and the common subway microbiome was determined. However, there were differences in microbiological and antibiotic-resistance profiles, depending on the station. The station's operational period since opening correlated with the taxonomic diversity and resistance of the identified bacteria. Moreover, differences between aerosol and surface bacterial communities were found at the two subway stations, indicating the importance of diversified sampling during the microbiome profiling of public areas. In this study, we also compared our data with previously published results obtained for the Moscow subway. Despite sample collection at different stations and seasons, we showed the presence of 15 common genera forming the core microbiome of the Moscow subway, which represents human commensal species, as well as widespread microorganisms from the surrounding environment.
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- 2022
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13. The rise and spread of the SARS-CoV-2 AY.122 lineage in Russia.
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Klink GV, Safina K, Nabieva E, Shvyrev N, Garushyants S, Alekseeva E, Komissarov AB, Danilenko DM, Pochtovyi AA, Divisenko EV, Vasilchenko LA, Shidlovskaya EV, Kuznetsova NA, Samoilov AE, Neverov AD, Popova AV, Fedonin GG, Akimkin VG, Lioznov D, Gushchin VA, Shchur V, and Bazykin GA
- Abstract
Background: Delta has outcompeted most preexisting variants of SARS-CoV-2, becoming the globally predominant lineage by mid-2021. Its subsequent evolution has led to emergence of multiple sublineages, many of which are well-mixed between countries., Aim: Here, we aim to study the emergence and spread of the Delta lineage in Russia., Methods: We use a phylogeographic approach to infer imports of Delta sublineages into Russia, and phylodynamic models to assess the rate of their spread., Results: We show that nearly the entire Delta epidemic in Russia has probably descended from a single import event despite genetic evidence of multiple Delta imports. Indeed, over 90% of Delta samples in Russia are characterized by the nsp2:K81N+ORF7a:P45L pair of mutations which is rare outside Russia, putting them in the AY.122 sublineage. The AY.122 lineage was frequent in Russia among Delta samples from the start, and has not increased in frequency in other countries where it has been observed, suggesting that its high prevalence in Russia has probably resulted from a random founder effect., Conclusion: The apartness of the genetic composition of the Delta epidemic in Russia makes Russia somewhat unusual, although not exceptional, among other countries.
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- 2021
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14. A Deep Look Into COVID-19 Severity Through Dynamic Changes in Blood Cytokine Levels.
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Kleymenov DA, Bykonia EN, Popova LI, Mazunina EP, Gushchin VA, Kolobukhina LV, Burgasova OA, Kruzhkova IS, Kuznetsova NA, Shidlovskaya EV, Divisenko EV, Pochtovyi AA, Bacalin VV, Smetanina SV, Tkachuk AP, Logunov DY, and Gintsburg AL
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- Acute-Phase Reaction blood, Antibodies, Viral immunology, COVID-19 pathology, Critical Care statistics & numerical data, Cytokine Release Syndrome pathology, Female, Humans, Immunoglobulin A blood, Immunoglobulin G blood, Immunoglobulin M blood, Male, Middle Aged, Prognosis, RNA, Viral analysis, Antibodies, Viral blood, COVID-19 mortality, Cytokine Release Syndrome blood, Cytokines blood, SARS-CoV-2 immunology, Severity of Illness Index
- Abstract
An excessive inflammatory response to SARS-CoV-2 is thought to be a major cause of disease severity and mortality in patients with COVID-19. Longitudinal analysis of cytokine release can expand our understanding of the initial stages of disease development and help to identify early markers serving as predictors of disease severity. In this study, we performed a comprehensive analysis of 46 cytokines (including chemokines and growth factors) in the peripheral blood of a large cohort of COVID-19 patients (n=444). The patients were classified into five severity groups. Longitudinal analysis of all patients revealed two groups of cytokines, characterizing the "early" and "late" stages of the disease course and the switch between type 1 and type 2 immunity. We found significantly increased levels of cytokines associated with different severities of COVID-19, and levels of some cytokines were significantly higher during the first three days from symptom onset (DfSO) in patients who eventually required intensive care unit (ICU) therapy. Additionally, we identified nine cytokines, TNF-α, IL-10, MIG, IL-6, IP-10, M-CSF, G-CSF, GM-CSF, and IFN-α2, that can be used as good predictors of ICU requirement at 4-6 DfSO., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kleymenov, Bykonia, Popova, Mazunina, Gushchin, Kolobukhina, Burgasova, Kruzhkova, Kuznetsova, Shidlovskaya, Divisenko, Pochtovyi, Bacalin, Smetanina, Tkachuk, Logunov and Gintsburg.)
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- 2021
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15. A Strategy for the Rapid Development of a Safe Vibrio cholerae Candidate Vaccine Strain.
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Karpov DS, Goncharenko AV, Usachev EV, Vasina DV, Divisenko EV, Chalenko YM, Pochtovyi AA, Ovchinnikov RS, Makarov VV, Yudin SM, Tkachuk AP, and Gushchin VA
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- Gene Transfer Techniques, Genes, Reporter, Genetic Engineering, Genome, Bacterial, Cholera Vaccines, Operon, Vibrio cholerae genetics
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Approximately 1/6 of humanity is at high risk of experiencing cholera epidemics. The development of effective and safe vaccines against Vibrio cholerae, the primary cause of cholera, is part of the public health measures to prevent cholera epidemics. Natural nontoxigenic V. cholerae isolates represent a source of new genetically improved and relatively safe vaccine strains. However, the genomic engineering of wild-type V. cholerae strains is difficult, and these strains are genetically unstable due to their high homologous recombination activity. We comprehensively characterized two V. cholerae isolates using genome sequencing, bioinformatic analysis, and microscopic, physiological, and biochemical tests. Genetic constructs were Gibson assembled and electrotransformed into V. cholerae . Bacterial colonies were assessed using standard microbiological and immunological techniques. As a result, we created a synthetic chromoprotein-expressing reporter operon. This operon was used to improve the V. cholerae genome engineering approach and monitor the stability of the genetic constructs. Finally, we created a stable candidate V. cholerae vaccine strain bearing a recA deletion and expressing the β-subunit of cholera toxin. Thus, we developed a strategy for the rapid creation of genetically stable and relatively safe candidate vaccine strains. This strategy can be applied not only to V. cholerae but also to other important human bacterial pathogens.
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- 2021
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16. Discovering the Potentials of Four Phage Endolysins to Combat Gram-Negative Infections.
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Vasina DV, Antonova NP, Grigoriev IV, Yakimakha VS, Lendel AM, Nikiforova MA, Pochtovyi AA, Remizov TA, Usachev EV, Shevlyagina NV, Zhukhovitsky VG, Fursov MV, Potapov VD, Vorobev AM, Aleshkin AV, Laishevtsev AI, Makarov VV, Yudin SM, Tkachuk AP, and Gushchin VA
- Abstract
Endolysin-based therapeutics are promising antibacterial agents and can successfully supplement the existing antibacterial drugs array. It is specifically important in the case of Gram-negative pathogens, e.g., ESKAPE group bacteria, which includes Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species, and are highly inclined to gain multiple antibiotic resistance. Despite numerous works devoted to the screening of new lytic enzymes and investigations of their biochemical properties, there are significant breaches in some aspects of their operating characteristics, including safety issues of endolysin use. Here, we provide a comprehensive study of the antimicrobial efficacy aspects of four Gram-negative bacteria-targeting endolysins LysAm24, LysAp22, LysECD7, and LysSi3, their in vitro and in vivo activity, and their biological safety. These endolysins possess a wide spectrum of action, are active against planktonic bacteria and bacterial biofilms, and are effective in wound and burn skin infection animal models. In terms of safety, these enzymes do not contribute to the development of short-term resistance, are not cytotoxic, and do not significantly affect the normal intestinal microflora in vivo . Our results provide a confident base for the development of effective and safe candidate dosage forms for the treatment of local and systemic infections caused by Gram-negative bacterial species., Competing Interests: NA, DV, AT, and VG are the authors but not the patent holders of the following patents issued according to the results of this work (RU): RU 2730613 C1 “Antibacterial composition (embodiments) and use of protein as antimicrobial agent directed against bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Salmonella typhi, and Staphylococcus haemolyticus (embodiments)”; RU 2730614 C1 “Antibacterial composition (embodiments) and use of protein as antimicrobial agent directed against bacteria P. aeruginosa, K. pneumoniae, Escherichia coli, Salmonella typhi, and Staphylococcus haemolyticus (embodiments)”; RU 2730615 C1 “Antibacterial composition (embodiments) and use of protein as antimicrobial agent directed against Gram-negative bacteria: P. aeruginosa, Acinetobacter baumannii, K. pneumoniae, and Salmonella typhi (embodiments)”; and RU 2730616 C1 “Antibacterial composition (embodiments) and use of protein as an antimicrobial agent directed against A. baumannii bacteria (embodiments).” The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vasina, Antonova, Grigoriev, Yakimakha, Lendel, Nikiforova, Pochtovyi, Remizov, Usachev, Shevlyagina, Zhukhovitsky, Fursov, Potapov, Vorobev, Aleshkin, Laishevtsev, Makarov, Yudin, Tkachuk and Gushchin.)
- Published
- 2021
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17. Contamination of Hospital Surfaces with Bacterial Pathogens under the Current COVID-19 Outbreak.
- Author
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Pochtovyi AA, Vasina DV, Kustova DD, Divisenko EV, Kuznetsova NA, Burgasova OA, Kolobukhina LV, Tkachuk AP, Gushchin VA, and Gintsburg AL
- Subjects
- Bacteria genetics, Disease Outbreaks, Hospitals, Humans, RNA, Ribosomal, 16S genetics, SARS-CoV-2, COVID-19
- Abstract
The SARS-CoV-2 pandemic remains a global health issue for several reasons, such as the low vaccination rates and a lack of developed herd immunity to the evolution of SARS-CoV-2, as well as its potential inclination to elude neutralizing antibodies. It should be noted that the severity of the COVID-19 disease is significantly affected by the presence of co-infections. Comorbid conditions are caused not only by pathogenic and opportunistic microorganisms but also by some representatives of the environmental microbiome. The presence of patients with moderate and severe forms of the disease in hospitals indicates the need for epidemiological monitoring of (1) bacterial pathogens circulating in hospitals, especially the ESKAPE group pathogens, and (2) the microbiome of various surfaces in hospitals. In our study, we used combined methods based on PCR and NGS sequencing, which are widely used for epidemiological monitoring. Through this approach, we identified the DNA of pathogenic bacteria ( Klebsiella pneumoniae , Pseudomonas aeruginosa , Staphylococcus aureus , CoNS, and Achromobacter spp.) on various surfaces. We also estimated the microbiome diversity of surfaces and identified the potential reservoirs of infections using 16S rRNA profiling. Although we did not assess the viability of identified microorganisms, our results indicate the possible risks of insufficient regular disinfection of surfaces, regardless of department, at the Infectious Diseases Hospital. Controlling the transmission of nosocomial diseases is critical to the successful treatment of COVID-19 patients, the rational use of antimicrobial drugs, and timely decontamination measures.
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- 2021
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18. Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants.
- Author
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Gushchin VA, Dolzhikova IV, Shchetinin AM, Odintsova AS, Siniavin AE, Nikiforova MA, Pochtovyi AA, Shidlovskaya EV, Kuznetsova NA, Burgasova OA, Kolobukhina LV, Iliukhina AA, Kovyrshina AV, Botikov AG, Kuzina AV, Grousova DM, Tukhvatulin AI, Shcheblyakov DV, Zubkova OV, Karpova OV, Voronina OL, Ryzhova NN, Aksenova EI, Kunda MS, Lioznov DA, Danilenko DM, Komissarov AB, Tkachuck AP, Logunov DY, and Gintsburg AL
- Abstract
Since the beginning of the 2021 year, all the main six vaccines against COVID-19 have been used in mass vaccination companies around the world. Virus neutralization and epidemiological efficacy drop obtained for several vaccines against the B.1.1.7, B.1.351 P.1, and B.1.617 genotypes are of concern. There is a growing number of reports on mutations in receptor-binding domain (RBD) increasing the transmissibility of the virus and escaping the neutralizing effect of antibodies. The Sputnik V vaccine is currently approved for use in more than 66 countries but its activity against variants of concern (VOC) is not extensively studied yet. Virus-neutralizing activity (VNA) of sera obtained from people vaccinated with Sputnik V in relation to internationally relevant genetic lineages B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 and Moscow endemic variants B.1.1.141 (T385I) and B.1.1.317 (S477N, A522S) with mutations in the RBD domain has been assessed. The data obtained indicate no significant differences in VNA against B.1.1.7, B.1.617.3 and local genetic lineages B.1.1.141 (T385I), B.1.1.317 (S477N, A522S) with RBD mutations. For the B.1.351, P.1, and B.1.617.2 statistically significant 3.1-, 2.8-, and 2.5-fold, respectively, VNA reduction was observed. Notably, this decrease is lower than that reported in publications for other vaccines. However, a direct comparative study is necessary for a conclusion. Thus, sera from "Sputnik V"-vaccinated retain neutralizing activity against VOC B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 as well as local genetic lineages B.1.1.141 and B.1.1.317 circulating in Moscow.
- Published
- 2021
- Full Text
- View/download PDF
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