Anti-enteric efficacy and mode of action of tridecanoic acid methyl ester isolated from Monochoria hastata (L.) Solms leaf.

Monochoria hastata (L.) Solms (family Pontederiaceae), an ethnomedicinal aquatic herb, is used to remedy several gastrointestinal diseases by various ethnic groups in India. The present study aimed to purify and characterize the antibacterial active ingredient against gastrointestinal (GI) diseases and its mode of action using in vitro experimental models. The active lead molecule in the ethyl acetate extract (EA-Mh) fraction has been purified and characterized through high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance (1H NMR), and electrospray ionization mass spectrometry (ESI-MS) methods. The anti-enteric efficacy has been evaluated against enteropathogenic Gram-positive and Gram-negative bacteria by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), lactate dehydrogenase (LDH), and scanning electron microscopy (SEM) studies. The synergistic and antagonistic studies were done on E. coli MTCC 723 using standard antibiotics (ampicillin and kanamycin, final conc. 50 µg/ml) in a sterilized 96-well micro-plate, incubated at 37 ℃ for 24 h. The chromatographic and spectroscopic analyses revealed the presence of tridecanoic acid methyl ester (TAME) in the bioactive fraction. The compound causes significant extracellular leakage activity by disrupting cellular morphology in the Enterococcus faecalis MCC 2041 T and Salmonella enterica serovar Typhimurium MTCC 98, at a dose of 375 µg/ml and 750 µg/ml, respectively. The SEM study shows a significant rupturing of E. coli and E. faecalis cells due to TAME induced autolysis. It has synergistic activity with ampicillin. The in silico molecular docking through the AutoDock Vina 4.2 and GROMACS (ver. 5.1) Charmm27 force field results showed that the TAME had a strong binding affinity Escherichia coli DNA Gyrase B (PDB ID: 5l3j.pdb) protein and caused conformational changes. Thus, the manuscript reports the first time on the characterization of TAME from this plant with a detailed antibacterial mode of action studies.

Inhibitory efficacy of RNA virus drugs against SARS-CoV-2 proteins: An extensive study.

Herein we have made a comprehensive analysis of inhibitory efficacy of 16 RNA virus drugs against RdRp, Mpro and PLpro proteins of SARS-CoV-2. Analysis of docked conformation revealed that Baloxavir marboxil (BMX) corresponds to the highest binding energy. Analysis of residue confirmed that BMX strongly interact with these three proteins involving H-bonding, ionic as well as hydrophobic interactions. Molecular dynamics simulation and analysis of parameters like RMSD, RMSF, binding energy confirmed noticeable conformational alternation with these proteins with makeable effect on RdRp. The potentially inhibitory action of BMX against these three proteins suggests the inhibition of overall transcription process of SARS-CoV-2. These observation along with the recently observed inhibitory action of BMX on influenza with clinically proven no side effects emphasizes to uncover the role of BMX by in-vitro and in-vivo analysis.