COVID-19 therapy: from myths to reality and hopes

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, is unprecedented for the 21st century and has already affected countries with a total population of billions of people. The number of infected has already surpassed 30 million people and the number of deaths has exceeded 1 million. Unfor-tunately, Russia is still one of the five countries with the largest number of infected people, although mortality from COVID-19 is significantly lower than in many other countries. Since the virus and the pathogenesis caused by it have a lot of new and unexpected features, high-tech and specific anti-viral drugs and vaccines have not yet been created. The most promising targets for future drug development are enzymes necessary for the life cycle of this particular virus (such as components of the replicase complex or viral proteases). Unexpected circumstances are pushing the evaluation of a number of previously developed and existing drugs directed toward other RNA viruses, some of which have already been shown effective in clinical trials against SARS-CoV-2. There is no doubt that soon prototypes of drugs of this class with higher specificity and effective-ness will be found. Another group of potential drugs are known drugs that are directed against various aspects of the pathogenesis caused by SARS-CoV-2, in particular, cytokine storm or coagulopathy. It should be emphasized that the genome of the virus encodes about 10 additional proteins, some of which may be related to unusual aspects of pathogenesis during COVID-19. Basic research should determine which of these proteins can be targets for specific therapy. Finally, the fact that neutralizing antibodies are found in the blood plasma of many patients and can be used for the prevention and treatment of COVID-19, indicates the potential of using recombinant neutralizing antibodies as drugs, and secondly, confirms the possibility of creating effective vaccines. This mini-review discusses therapeutic approaches and the status of clinical trials using drugs that already existed before the pandemic and were originally developed against other infectious agents or for the treatment of autoimmune pathologies. These drugs are part of today's arsenal in therapeutic protocols and are used in an attempt to cope with the COVID-19 epidemic in different countries

In Vitro Cytotoxicity of CdSe/ZnS Quantum Dots and Their Interaction with Biological Systems

Semiconductor nanocrystals (quantum dots, QDs) have a wide range of potential application in multiplexed tissue and cell imaging, and for in vivo molecular diagnostics and therapy. Therefore studying of the toxicity of QDs and their influence on various cellular processes in vitro is necessary to understand their interaction with living systems.; The paper presents the results of studies on the evaluation of CdSe/ZnS QD cytotoxicity, as well as the results of studying their interaction with freshly prepared human monocytes in vitro. Keywords: Quantum dots, semiconductor nanocrystals, cytotoxicity, in vitro models, monocytes

Cytotoxicity of Polyelectrolyte Microcapsules Encoded with Semiconductor Nanocrystals

Polyelectrolyte microcapsules are promising carriers of drugs and diagnostic agents for designing targeted and controlled delivery systems design. The use of quantum dots (QDs) as fluorescent labels in bioimaging is a promising approach to bioimaging tool development. The potential toxicity of QDs makes their applicability as fluorescent labels in vivo questionable. Therefore, the cytotoxicity of polyelectrolyte microcapsules encoded with semiconductor nanocrystals has been investigated. Keywords: Polyelectrolyte microcapsules, semiconductor nanocrystals, cytotoxicity, theranostic agents

Fine-tuning of Silica Coating Procedure for Preparation of Biocompatible and Bright Pbs/Sio2 Qds

Near-infrared semiconductor PbS quantum dots (QDs) with emission in biological transparency window are promising material for in vivo biolabelling and deep-tissue imaging of biological specimen. Among various approaches that render initially hydrophobic and toxic QDs biocompatible, the growth of a silica shell on the QD surface represents an efficient method to minimize QD toxicity. Nevertheless, it is important to preserve QDs emission properties after the silica coating procedure. Here we report on the optimal parameters of this procedure which allow to obtain a stable silica shell and maintain the optical properties of initial PbS QDs. Furthermore, we show that PbS QDs with the optimal SiO2 shell retain their luminescence quantum yield even after condensation into a solid film. Thus, our procedure can become a basis in development of bright, receptor-targeted NIR fluorescent probes for in vivo tumor imaging. Keywords: quantum dot, SiO2 shell, bioimagin

Highly Stable, Water-Soluble CdSe/ZnS/CdS/ZnS Quantum Dots with Additional SiO2 shell

Quantum dots (QDs) are fluorescent nanocrystals extensively used today in research and applications. They attract much interest due to the high photostability and fluorescence quantum yields close to 100%. The best QDs are made by synthesis in organic media, and they have to be transferred into aqueous solutions if biomedical applications are concerned. An advanced method for rendering QDs water-soluble is to coat them with hydrophilic SiO2 -layer. However, growing a silica shell with a predetermined thickness is a problem, because uncertain values of the molar extinction coefficients (ε) of core/shell QDs made it impossible to calculate precise yields of the chemical reactions involved. Here we suggest an approach to solving this problem by constructing the structural models of per se and silica-coated QDs followed by measuring ε in a course of the QD synthesis, thus carrying out precise quantitative reactions. Proceeding in such a way, we prepared the CdSe/ZnS/CdS/ZnS QDs with the structure predicted by the model and coated by silica shell. Prepared QDs are characterized by a narrow size distribution and the same fluorescence parameters as the original QDs in the organic medium. Developed approach permitted efficient QDs water-solubilisation and preparation of stable nanoparticles for plethora of biomedical applications.     Keywords: Quantum dots, QD, silica shell, core-shel

IL

Interleukin 4 (IL-4) was shown to be tumor-promoting in full carcinogenesis studies using 3-methylcholanthrene (MCA). Because heretofore the role of IL-4 in DMBA/TPA (9,10-dimethyl-1,2-benz-anthracene/12-O-tetradecanoylphorbol-13-acetate) two-stage carcinogenesis was not studied, we performed such experiments using either IL-4(−/−) or IL-4Rα(−/−) mice. We found that IL-4Rα(−/−) but not IL-4(−/−) mice have enhanced papilloma formation, suggesting that IL-13 may be involved. Indeed, IL-13(−/−) mice developed more papillomas after exposure to DMBA/TPA than their heterozygous IL-13-competent littermate controls. However, when tested in a full carcinogenesis experiment, exposure of mice to 25 μg of MCA, both IL-13(−/−) and IL-13(+/−) mice led to the same incidence of tumors. While IL-4 enhances MCA carcinogenesis, it does not play a measurable role in our DMBA/TPA carcinogenesis experiments. Conversely, IL-13 does not affect MCA carcinogenesis but protects mice from DMBA/TPA carcinogenesis. One possible explanation is that IL-4 and IL-13, although they share a common IL-4Rα chain, regulate signaling in target cells differently by employing distinct JAK/STAT-mediated signaling pathways downstream of IL-13 or IL-4 receptor complexes, resulting in different inflammatory transcriptional programs. Taken together, our results indicate that the course of DMBA/TPA- and MCA-induced carcinogenesis is affected differently by IL-4 versus IL-13-mediated inflammatory cascades