ABSTRACT
Efficient conditions for the synthesis of nitrogen-containing heterocyclic derivatives of (1R,3S)(+)-camphoric acid were selected. A series of heterocyclic compounds based on (+)-camphoric acid bearing pharmacophoric fragments was synthesized using the developed methodology. The compounds were tested for their antiviral activity against SARS-CoV-2 and H1N1 influenza viruses, and efficient inhibitors were identified that are of significant interest for further studies. The stability of the compounds and pharmaco-kinetics of the leader compound were studied when administered intragastrically and intramuscularly to mice at a dose of 200 mg kg-1 using the HPLC-MS/MS method.
ABSTRACT
Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC-MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.