Publications by authors named "Ishmukhametov A"

The interaction of inactivated poliovirus vaccine strains with oriented antibodies immobilized to protein A via Fc fragments has been investigated. Using an SPR biosensor, the kinetic and equilibrium parameters of the interaction of vaccine attenuated polioviruses of the Sabin strains type 1 and type 2, inactivated by various methods were determined. The strongest interaction was observed between polyclonal antibodies to Sabin strain type 2 poliovirus and Sabin strain type 2 poliovirus inactivated with β-propiolactone, KD = 1.

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Vaccination is the most effective strategy for fighting viral diseases, with both live and inactivated vaccines remaining crucial despite advancements in subunit vaccine technologies. A key player in vaccine production is the Vero cell line, derived from the kidney cells of the African green monkey, which is essential for manufacturing vaccines against diseases like polio, rabies, yellow fever, and COVID-19. The efficiency of Vero cell cultivation directly impacts vaccine production, often utilizing bioreactors ranging from small (1-10 L) to large (up to several thousand liters).

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In this article we discuss characteristics of fusion protein-based SARS-CoV-2 vaccines. We focus on recombinant vaccine antigens comprising fusion proteins consisting of combinations of SARS-CoV-2-derived antigens or peptides or combinations of SARS-CoV-2 antigens/peptides with SARS-CoV-2-unrelated proteins/peptides. These fusion proteins are made to increase the immunogenicity of the vaccine antigens and/or to enable special targeting of the immune system.

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: We evaluate the immunotherapeutic potential of the yellow fever virus vaccine strain 17D (YFV 17D) for intratumoral therapy of pancreatic cancer in mice. : The cytopathic effect of YFV 17D on mouse syngeneic pancreatic cancers cells were studied both in vitro and in vivo and on human pancreatic cancers cells in vitro. : YFV 17D demonstrated a strong cytopathic effect against human cancer cells in vitro.

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Combined viral and photodynamic therapy for oncological diseases has great potential to treat aggressive tumors such as glioblastomas. A conjugate of vesicular stomatitis virus (VSV) with protoporphyrin IX was prepared, and its oncolytic effects were studied and compared to the effects of the individual components. The VSV showed an oncolytic effect on glioblastoma cell lines T98G and LN229 at a virus titer of 10 TCID/mL.

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Hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) are the most common viral diseases in Russia. HFRS is caused by six different types of hantaviruses: Hantaan, Amur, Seoul, Puumala, Kurkino, and Sochi, which are transmitted to humans through small mammals of the Muridae and Cricetidae families. TBE is caused by viruses belonging to five different phylogenetic subtypes.

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Article Synopsis
  • * A study in Russia examined 574 hospitalized children under 18 with COVID-19 from January 2022 to March 2023, finding about one-third had coinfections, predominantly adenovirus and bacterial infections.
  • * Results indicated that while viral coinfections led to higher fevers and bronchitis, bacterial coinfections resulted in longer illnesses and increased pneumonia, suggesting that seasonal viruses may have been more harmful to children during the Omicron wave than SARS-CoV-2 alone.
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Common marmoset (, CM) is a New World primate species that is of interest for preclinical trials of immunobiological products. In this study, we describe the approaches to long-term laboratory breeding and maintenance of CMs. We also establish the reference values of the main complete blood count and serum chemistry parameters evaluated during preclinical trials of immunobiological products and describe the histological characteristics of CM lymphoid organs during the development of post-vaccination immune response.

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Non-human primates, due to their similarities in immune response to humans, are the preferred model for studying infectious processes and any associated cognitive impairments. Behavioral tests are indispensable for investigating pathogenesis in neuroinfections, especially those that do not manifest with noticeable clinical symptoms, as well as in the transition to a chronic form of the disease. Modeling viral infection requires specialized experimental conditions.

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Article Synopsis
  • X-ray structures of coronavirus drug targets were rapidly acquired during the early COVID-19 pandemic, especially focusing on the main protease (Mpro) of SARS-CoV-2, which is crucial for developing direct antiviral drugs.
  • A systematic, semi-automated method was developed to select the best ensemble of Mpro structures for virtual screening of potential inhibitors, as the selection process was complex.
  • This method was validated against existing approaches and led to the discovery of new thienopyrimidinone derivatives that effectively inhibit the Mpro enzyme.
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Electrochemical profiling of formaldehyde-inactivated poliovirus particles demonstrated a relationship between the D-antigen concentration and the intensity of the maximum amplitude currents of the poliovirus samples. The resultant signal was therefore identified as electrochemical oxidation of the surface proteins of the poliovirus. Using registration of electrooxidation of amino acid residues of the capsid proteins, a comparative electrochemical analysis of poliovirus particles inactivated by electrons accelerated with doses of 5 kGy, 10 kGy, 15 kGy, 25 kGy, 30 kGy at room temperature was carried out.

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Evolutionary potential of viruses can result in outbreaks of well-known viruses and emergence of novel ones. Pharmacological methods of intervening the reproduction of various less popular, but not less important viruses are not available, as well as the spectrum of antiviral activity for most known compounds. In the framework of chemical biology paradigm, characterization of antiviral activity spectrum of new compounds allows to extend the antiviral chemical space and provides new important structure-activity relationships for data-driven drug discovery.

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Tick-borne encephalitis virus (TBEV) causes a severe disease, tick-borne encephalitis (TBE), that has a substantial epidemiological importance for Northern Eurasia. Between 10,000 and 15,000 TBE cases are registered annually despite the availability of effective formaldehyde-inactivated full-virion vaccines due to insufficient vaccination coverage, as well as sporadic cases of vaccine breakthrough. The development of improved vaccines would benefit from the atomic resolution structure of the antigen.

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The EMCV L and 2A proteins are virulence factors that counteract host cell defense mechanisms. Both L and 2A exhibit antiapoptotic properties, but the available data were obtained in different cell lines and under incomparable conditions. This study is aimed at checking the role of these proteins in the choice of cell death type in three different cell lines using three mutants of EMCV lacking functional L, 2A, and both proteins together.

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X-ray imaging of virus particles at the European XFEL could eventually allow their complete structures to be solved, potentially approaching the resolution of other structural virology methods. To achieve this ambitious goal with today's technologies, about 1 ml of purified virus suspension containing at least 10 particles per millilitre is required. Such large amounts of concentrated suspension have never before been obtained for enveloped viruses.

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Introduction: Infection of cells with encephalomyocarditis virus type 1 (EMCV-1, ) is accompanied by suppression of cellular protein synthesis. The main role in the inhibition of cellular translation is assigned to the L and 2A «security» proteins. The mechanism of the possible influence of the L protein on cellular translation is unknown.

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Introduction: Flaviviruses, possessing natural neurotropicity could be used in glioblastoma therapy using attenuated strains or as a delivery system for antitumor agents in an inactivated form.

Objective: To investigate the sensitivity of glioblastoma and pancreatic carcinoma cell lines to vaccine strains of yellow fever and tick-borne encephalitis viruses.

Materials And Methods: Cell lines: glioblastoma GL-6, T98G, LN-229, pancreatic carcinoma MIA RaCa-2 and human pancreatic ductal carcinoma PANC-1.

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Tick-borne encephalitis virus (TBEV) and Powassan virus (POWV) are neurotropic tick-borne orthoflaviviruses. They cause mostly asymptomatic infections in hosts, but severe forms with CNS involvement can occur. Studying the early stages of viral infections in humans is challenging, and appropriate animal models are essential for understanding the factors determining the disease severity and for developing emergency prophylaxis and treatment options.

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Article Synopsis
  • The addition of lipophilic groups to nucleoside analogues enhances their antiviral potency, particularly against viruses like TBEV and EV-A71.
  • Researchers synthesized a series of N-benzyladenosine analogues using specific cross-coupling methods to analyze their effectiveness against different flaviviruses and enteroviruses.
  • The compounds showed strong inhibition of flavivirus replication at low concentrations, targeting viral RNA synthesis while displaying minimal cytotoxicity, but they did not affect enterovirus reproduction, suggesting a unique mechanism focused on flaviviruses.
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COVID-19 is a systemic inflammatory disease initiated by SARS-CoV-2 virus infection. Multiple vaccines against the Wuhan variant of SARS-CoV-2 have been developed including a whole virion beta-propiolactone-inactivated vaccine based on the B.1.

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The main approach to preventing tick-borne encephalitis (TBE) is vaccination. Formaldehyde-inactivated TBE vaccines have a proven record of safety and efficiency but have never been characterized structurally with atomic resolution. We report a cryoelectron microscopy (cryo-EM) structure of the formaldehyde-inactivated TBE virus (TBEV) of Sofjin-Chumakov strain representing the Far-Eastern subtype.

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Traditional antiviral vaccines are currently created by inactivating the virus chemically, most often using formaldehyde or β-propiolactone. These approaches are not optimal since they negatively affect the safety of the antigenic determinants of the inactivated particles and require additional purification stages. The most promising platforms for creating vaccines are based on pseudoviruses, i.

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Oncolytic viruses offer a promising approach to tumor treatment. These viruses not only have a direct lytic effect on tumor cells but can also modify the tumor microenvironment and activate antitumor immunity. Due to their high pathogenicity, flaviviruses have often been overlooked as potential antitumor agents.

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We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial phase I/II of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in volunteers aged 18-60 and open multi-center comparative phase IIb clinical trial in volunteers aged 60 years and older. The safety of the vaccine was assessed in 400 volunteers in the 18-60 age cohort who received two doses of the vaccine (n = 300) or placebo (n = 100) and in 200 volunteers in 60+ age cohort all of whom received three doses of the vaccine. The studied vaccine has shown good tolerability and safety.

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During 2000-2022, a total of 69 of Russia's 85 administrative regions reported 164,580 hemorrhagic fever with renal syndrome (HFRS) cases, with an annual average rate of 4.9 cases/100,000 population (10 popul.).

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