To facilitate the detection and management of potential clinical antiviral resistance, in vitro selection of drug-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) against the virus M inhibitor nirmatrelvir (Paxlovid active component) was conducted. Six M mutation patterns containing T304I alone or in combination with T21I, L50F, T135I, S144A, or A173V emerged, with A173V+T304I and T21I+S144A+T304I mutations showing >20-fold resistance each. Biochemical analyses indicated inhibition constant shifts aligned to antiviral results, with S144A and A173V each markedly reducing nirmatrelvir inhibition and M activity.
View Article and Find Full Text PDFObesity is a socially significant disease that is characterized by a disproportionate accumulation of fat. It is also associated with chronic inflammation, cancer, diabetes, and other comorbidities. Investigating biomarkers and pathological processes linked to obesity is especially vital for young individuals, given their increased potential for lifestyle modifications.
View Article and Find Full Text PDFThe fact of global climate change is generally recognized by the world scientific community. However, the spatial distribution of climatic parameters is very heterogeneous. In this regard, studies of the local response of individual territories to global climate change are of particular importance.
View Article and Find Full Text PDFRecently, the concept of a mass spectrometric blood metabogram was introduced, which allows the analysis of the blood metabolome in terms of the time, cost, and reproducibility of clinical laboratory tests. It was demonstrated that the components of the metabogram are related groups of the blood metabolites associated with humoral regulation; the metabolism of lipids, carbohydrates, and amines; lipid intake into the organism; and liver function, thereby providing clinically relevant information. The purpose of this work was to evaluate the relevance of using the metabogram in a disease.
View Article and Find Full Text PDFType 2 diabetes mellitus (T2DM) is a widespread disease with a high risk of cardiovascular complications, disability and mortality. The progression of T2DM is closely related to lipid metabolism disorders, caused both by insufficient intake of polyunsaturated fatty acids (PUFAs), and by a violation of their endogenous metabolism. Desaturase enzymes, FADS1/2, are involved in the regulation of PUFA metabolism.
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