COMPUTER-AIDED PREDICTION OF MULTITARGET PROFILES: CASE STUDIES FOR CLOZAPINE AND DASATINIB

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Cyclobutane-Containing Alkaloids: Origin, Synthesis, and Biological Activities

Present review describes research on novel natural cyclobutane-containing alkaloids isolated from terrestrial and marine species. More than 60 biological active compounds have been confirmed to have antimicrobial, antibacterial, antitumor, and other activities. The structures, synthesis, origins, and biological activities of a selection of cyclobutane-containing alkaloids are reviewed. With the computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of cyclobutane-containing alkaloids as an important source of leads for drug discovery

Rationale for use mefloquine for COVID-19 treatment

Currently, the use of mefloquine in patients with COVID-19 does not have sufficient scientific justification and, given the unfavorable efficacy and safety profile, cannot be considered for routine use in clinical practice

HOW SHOULD ONE USE AVAILABLE DATA TO BE SUCCESSFUL IN COMPUTER-AIDED SEARCH FOR NOVEL KINASE INHIBITORS?

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PREDICTION OF THE METABOLIC NETWORK FOR XENOBIOTICS IN THE HUMAN ORGANISM

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Transcriptome-based analysis of human peripheral blood reveals regulators of immune response in different viral infections

IntroductionThere are difficulties in creating direct antiviral drugs for all viruses, including new, suddenly arising infections, such as COVID-19. Therefore, pathogenesis-directed therapy is often necessary to treat severe viral infections and comorbidities associated with them. Despite significant differences in the etiopathogenesis of viral diseases, in general, they are associated with significant dysfunction of the immune system. Study of common mechanisms of immune dysfunction caused by different viral infections can help develop novel therapeutic strategies to combat infections and associated comorbidities.MethodsTo identify common mechanisms of immune functions disruption during infection by nine different viruses (cytomegalovirus, Ebstein-Barr virus, human T-cell leukemia virus type 1, Hepatitis B and C viruses, human immunodeficiency virus, Dengue virus, SARS-CoV, and SARS-CoV-2), we analyzed the corresponding transcription profiles from peripheral blood mononuclear cells (PBMC) using the originally developed pipeline that include transcriptome data collection, processing, normalization, analysis and search for master regulators of several viral infections. The ten datasets containing transcription data from patients infected by nine viruses and healthy people were obtained from Gene Expression Omnibus. The analysis of the data was performed by Genome Enhancer pipeline.ResultsWe revealed common pathways, cellular processes, and master regulators for studied viral infections. We found that all nine viral infections cause immune activation, exhaustion, cell proliferation disruption, and increased susceptibility to apoptosis. Using network analysis, we identified PBMC receptors, representing proteins at the top of signaling pathways that may be responsible for the observed transcriptional changes and maintain the current functional state of cells.DiscussionThe identified relationships between some of them and virus-induced alteration of immune functions are new and have not been found earlier, e.g., receptors for autocrine motility factor, insulin, prolactin, angiotensin II, and immunoglobulin epsilon. Modulation of the identified receptors can be investigated as one of therapeutic strategies for the treatment of severe viral infections

WAY2DRUG CHEMINFORMATICS PLATFORM FOR DRUG REPURPOSING

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Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

Depression and schizophrenia are two highly prevalent and severely debilitating neuropsychiatric disorders. Both conventional antidepressant and antipsychotic pharmacotherapies are often inefficient clinically, causing multiple side effects and serious patient compliance problems. Collectively, this calls for the development of novel drug targets for treating depressed and schizophrenic patients. Here, we discuss recent translational advances, research tools and approaches, aiming to facilitate innovative drug discovery in this field. Providing a comprehensive overview of current antidepressants and antipsychotic drugs, we also outline potential novel molecular targets for treating depression and schizophrenia. We also critically evaluate multiple translational challenges and summarize various open questions, in order to foster further integrative cross-discipline research into antidepressant and antipsychotic drug development. © 2023 by the authors.075-15-2021-684; 857600; 122030100170-5; Suzhou University of Science and Technology; State Committee of Science, SCS: N 10-14/23-I/YSMUThis work was supported by the Republic of Armenia State Committee of Science (N 10-14/23-I/YSMU) and the European Union-funded H2020 COBRAIN project (857600). The funders had no role in the design, analyses and interpretation of the submitted study, or decision to publish.Computer-aided prediction of biological activity in this pharmacotherapeutic field (A.A.L. and V.V.P.) was overviewed within the framework of the Program for Basic Research in the Russian Federation for a long-term period (2021–2030) (project 122030100170-5). The research partially used the facilities and equipment of the Resource Fund of Applied Genetics MIPT (support grant 075-15-2021-684). A.V.K. is supported by St. Petersburg State University 2023 budget assignment funds. T.O.K. is supported by Neurobiology program of Sirius University of Science and Technology 2023 research budget funds. The authors thank Hasmik Harutyunyan (COBRAIN Center, Yerevan State Medical University) for help with graphical illustrations

Current and future use of umifenovir in patients with COVID-19

At the time of print, the evidence for using umifenovir in COVID-19 is mainly theoretical. The published clinical trials have contradicting results. The decision to use umifenovir in COVID-19 should be individualized, considering the “experimental” nature of this treatment