Structural analysis of a water insoluble polysaccharide from pearl millet and evaluating its prebiotic activity.

Epidemiological studies have shown an inverse correlation between dietary intake of prebiotics and the risk of chronic diseases. Pearl millet is a potential economic source to develop a new class of prebiotics in the form of its polysaccharide. In the present study, the chemical structure of a water insoluble homopolysaccharide (PMG), and its prebiotic properties were investigated. The structure of PMG was elucidated on the basis of total hydrolysis, methylation analysis, and 1D/2D NMR (1H, 13C, DEPT-135, HSQC, DQF-COSY, NOESY and ROESY) experiments. The results indicated that PMG was a glucan with an average molecular weight ~ 361 kDa having a backbone of (1 â†’ 3) α-d-glucopyranosyl residues. Hydrolysis of PMG by salivary and pancreatic α amylase was 1.75 % ± 0.34 and 1.99 % ± 0.18 respectively. A positive prebiotic score of PMG with both L. acidophilus and L. brevis (0.446 ± 0.031 & 0.427 ± 0.016) hints towards its prebiotic potential. These observations suggest that PMG might be used as a potential prebiotic component in the food and pharmaceutical applications.

Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections generate approximately one million virions per day, and the majority of available antivirals are ineffective against it due to the virus's inherent genetic mutability. This necessitates the investigation of concurrent inhibition of multiple SARS-CoV-2 targets. We show that fortunellin (acacetin 7-O-neohesperidoside), a phytochemical, is a promising candidate for preventing and treating coronavirus disease (COVID-19) by targeting multiple key viral target proteins. Fortunellin supports protective immunity while inhibiting pro-inflammatory cytokines and apoptosis pathways and protecting against tissue damage. Fortunellin is a phytochemical found in Gojihwadi kwath, an Indian traditional Ayurvedic formulation with an antiviral activity that is effective in COVID-19 patients. The mechanistic action of its antiviral activity, however, is unknown. The current study comprehensively evaluates the potential therapeutic mechanisms of fortunellin in preventing and treating COVID-19. We have used molecular docking, molecular dynamics simulations, free-energy calculations, host target mining of fortunellin, gene ontology enrichment, pathway analyses, and protein-protein interaction analysis. We discovered that fortunellin reliably binds to key targets that are necessary for viral replication, growth, invasion, and infectivity including Nucleocapsid (N-CTD) (-54.62 kcal/mol), Replicase-monomer at NSP-8 binding site (-34.48 kcal/mol), Replicase-dimer interface (-31.29 kcal/mol), Helicase (-30.02 kcal/mol), Papain-like-protease (-28.12 kcal/mol), 2'-O-methyltransferase (-23.17 kcal/mol), Main-protease (-21.63 kcal/mol), Replicase-monomer at dimer interface (-22.04 kcal/mol), RNA-dependent-RNA-polymerase (-19.98 kcal/mol), Nucleocapsid-NTD (-16.92 kcal/mol), and Endoribonuclease (-16.81 kcal/mol). Furthermore, we identify and evaluate the potential human targets of fortunellin and its effect on the SARS-CoV-2 infected tissues, including normal-human-bronchial-epithelium (NHBE) and lung cells and organoids such as pancreatic, colon, liver, and cornea using a network pharmacology approach. Thus, our findings indicate that fortunellin has a dual role; multi-target antiviral activities against SARS-CoV-2 and immunomodulatory capabilities against the host.