Acetate and succinate benefit host muscle energetics as exercise-associated post-biotics.

Recently, the gut microbiome has emerged as a potent modulator of exercise-induced systemic adaptation and appears to be crucial for mediating some of the benefits of exercise. This study builds upon previous evidence establishing a gut microbiome-skeletal muscle axis, identifying exercise-induced changes in microbiome composition. Metagenomics sequencing of fecal samples from non-exercise-trained controls or exercise-trained mice was conducted. Biodiversity indices indicated exercise training did not change alpha diversity. However, there were notable differences in beta-diversity between trained and untrained microbiomes. Exercise significantly increased the level of the bacterial species Muribaculaceae bacterium DSM 103720. Computation simulation of bacterial growth was used to predict metabolites that accumulate under in silico culture of exercise-responsive bacteria. We identified acetate and succinate as potential gut microbial metabolites that are produced by Muribaculaceae bacterium, which were then administered to mice during a period of mechanical overload-induced muscle hypertrophy. Although no differences were observed for the overall muscle growth response to succinate or acetate administration during the first 5 days of mechanical overload-induced hypertrophy, acetate and succinate increased skeletal muscle mitochondrial respiration. When given as post-biotics, succinate or acetate treatment may improve oxidative metabolism during muscle hypertrophy.

In-silico analysis of the inhibition of the SARS-CoV-2 main protease by some active compounds from selected African plants.

OBJECTIVES: Over the years, Azadirachta indica, Mangifera indica, and Moringa oleifera have been shown to possess some antiviral characteristics. This study applies molecular docking techniques to assess inhibitory effects of some bioactive compounds from the plants mentioned above against the main protease (Mpro), a key protein involved in SARS-CoV-2 replication. Furthermore, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles for screened compounds were predicted in silico. METHODS: The crystal structure of Mpro was retrieved from the Protein Data Bank, while the plant bioactive compounds were retrieved from Pubchem. Drug-likeness of the selected compounds and a control drug (hydroxychloroquine) were assessed, and the compounds that satisfied the drug-likeness rule were docked against Mpro. The docked complexes were analyzed using LigPlot and the protein-ligand profiler server. The top five compound hits were subjected to ADMET screening using the ADMETSar server. RESULTS: A total of 17 out of 22 screened compounds passed Lipinski's assessment. Additionally, the most active compounds from the investigated plants exhibited relative inhibitory potentials against Mpro compared with hydroxychloroquine, which alludes to their possible involvement in inhibiting the SARS-CoV-2 main protease replication process. CONCLUSIONS: In our study, most of the active phytocomponents of the investigated plants exhibited relative inhibitory potentials against Mpro of SARS-CoV-2 and preferred pharmacological features when compared with hydroxychloroquine. These findings indicate these compounds are potentially antiviral candidates against SARS-CoV-2.