Publications by authors named "Dmitriy Shcherbakov"

Antibodies are complex protein structures, and producing them using eukaryotic expression systems presents significant challenges. One frequently overlooked aspect of expression vectors is the nucleotide sequence encoding the signal peptide, which plays a pivotal role in facilitating the secretion of recombinant proteins. This study presents the development of an integrative vector, pVEAL3, for expressing full-length recombinant monoclonal antibodies in mammalian cells.

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Heterologous protein expression often faces significant challenges, particularly when the target protein has posttranslational modifications, is toxic, or is prone to misfolding. These issues can result in low expression levels, aggregation, or even cell death. Such problems are exemplified by the expression of phospholipase p37, a critical target for chemotherapeutic drugs against pathogenic human orthopoxviruses, including monkeypox and smallpox viruses.

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The annual number of reported human cases of flavivirus infections continues to increase. Measures taken by local healthcare systems and international organizations are not fully successful. In this regard, new approaches to treatment and prevention of flavivirus infections are relevant.

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Article Synopsis
  • The rise of filovirus outbreaks in Africa has created an urgent need for effective antiviral treatments.
  • Researchers synthesized and tested various derivatives of two compounds, (+)-fenchol and (-)-isopinocampheol, discovering that those with an N-alkylpiperazine cycle showed the strongest antiviral activity against specific viruses.
  • The antiviral effects of these compounds likely come from their ability to bind to surface glycoproteins of the viruses and their lysosomotropic properties, indicating they could potentially be dual-action agents worth further investigation.
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Antibodies are protein molecules whose primary function is to recognize antigens. However, recent studies have demonstrated their ability to hydrolyze specific substrates, such as proteins, oligopeptides, and nucleic acids. In 2023, two separate teams of researchers demonstrated the proteolytic activity of natural plasma antibodies from COVID-19 convalescents.

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In this study, we characterized recombinant hemagglutinin (HA) of influenza A (H5N8) virus produced in Chinese hamster ovary cells (CHO-K1s). Immunochemical analysis showed that the recombinant hemagglutinin was recognized by the serum of ferrets infected with influenza A (H5N8) virus, indicating that its antigenic properties were retained. Two groups of Balb/c mice were immunized with intramuscular injection of recombinant hemagglutinin or propiolactone inactivated A/Astrakhan/3212/2020 (H5N8) influenza virus.

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Article Synopsis
  • The research focuses on finding effective agents against coronaviruses, specifically by synthesizing thiazolo-thiophenes based on usnic acid to inhibit SARS-CoV-2's main protease.
  • Certain modifications of the thiophene groups showed moderate antiviral activity, while others had no effect, with kinetic parameters evaluated for the most promising compound.
  • The most active compound exhibited strong binding to the protease and effective antiviral activity against various SARS-CoV-2 strains, aligning molecular dynamics results with experimental findings.
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  • A new series of heterocyclic compounds featuring a specific bicyclic structure were created and tested for biological activity.
  • The synthesis involved a Cu(I) catalyzed cycloaddition using starting materials that included a specialized alkyne and various nitrogen-containing azides.
  • Some of these compounds showed promising antiviral effects against Marburg and Ebola viruses, and their effectiveness may be linked to their ability to target lysosomes and their hydrophobic interactions.
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Despite the long history of use and the knowledge of the genetics and biochemistry of , problems are still possible in obtaining a soluble form of recombinant proteins in this system. Although, soluble protein can be obtained both in the cytoplasm and in the periplasm of the bacterial cell. The latter is a priority strategy for obtaining soluble proteins.

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The fusion of viral and cell membranes is one of the basic processes in the life cycles of viruses. A number of enveloped viruses confer fusion of the viral envelope and the cell membrane using surface viral fusion proteins. Their conformational rearrangements lead to the unification of lipid bilayers of cell membranes and viral envelopes and the formation of fusion pores through which the viral genome enters the cytoplasm of the cell.

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Article Synopsis
  • * The study assessed how these derivatives inhibit the main protease of SARS-CoV-2 and their effectiveness against a pseudoviral system showcasing the virus's glycoprotein S.
  • * Findings indicated that usnic acid and its derivatives bind to a specific site on the glycoprotein S, suggesting a potential mechanism for their antiviral action.
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Candidates to being inhibitors of the main protease (Mpro) of SARS-CoV-2 were selected from the database of Voronezh State University using molecular modeling. The database contained approximately 19,000 compounds represented by more than 41,000 ligand conformers. These ligands were docked into Mpro using the SOL docking program.

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Flaviviruses are single-stranded RNA viruses that have emerged in recent decades and infect up to 400 million people annually, causing a variety of potentially severe pathophysiological processes including hepatitis, encephalitis, hemorrhagic fever, tissues and capillaries damage. The family is represented by four genera comprising 89 known virus species. There are no effective therapies available against many pathogenic flaviviruses.

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In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study the inhibition of the re-receptor-binding domain of protein S.

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  • Researchers tested the antiviral effectiveness of Arbidol (Umifenovir) against SARS-CoV-2 using a simulated viral system with the virus's spike protein.
  • The study identified multiple binding sites for Arbidol on the spike protein and noted that Arbidol's binding affects the protein's structural flexibility and interaction with enzymes.
  • The findings suggest that Arbidol can bind to various parts of the spike protein, contributing to its antiviral properties, which could aid in developing effective treatments targeting the virus's entry into cells.
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For the first time, derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine) were proposed as potential inhibitors of the SARS-CoV-2 main viral protease (3-chymotrypsin-like, 3CLpro).

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Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. This study aims to develop a reliable methodology for a rational aptamer in silico et vitro design.

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To date, the 'one bug-one drug' approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus.

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In this study, we screened a large library of (+)-camphor and (-)-borneol derivatives to assess their filovirus entry inhibition activities using pseudotype systems. Structure-activity relationship studies revealed several compounds exhibiting submicromolar IC values. These compounds were evaluated for their effect against natural Ebola virus (EBOV) and Marburg virus.

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