Journal of Biomolecular Structure and Dynamics

This study examines the nutritional composition, phytochemical profiling, and antioxidant, antidiabetic, and anti-inflammatory potential of a methanolic extract of Spilanthes filicaulis leaves (MESFL) via in vitro, ex vivo, and in silico studies. In vitro antioxidant, antidiabetic, and anti-inflammatory activities were examined. In the ex vivo study, liver tissues were subjected to FeSO 4-induced oxidative damage and treated with varying concentrations of MESFL. MESFL contains a reasonable amount of nitrogen-free extract, moisture, ash content, crude protein, and fat, with a lesser amount of crude fiber. According to GC-MS analysis, MESFL contains ten compounds, the most abundant of which are 13-octadecenal and Ar-tumerone. In this study, MESFL demonstrated anti-inflammatory activities via membrane stabilizing properties, proteinase inhibition, and inhibition of protein denaturation (IC 50 ¼ 72.75 ± 11.06 mg/mL). MESFL also strongly inhibited both a-amylase (IC 50 ¼ 307.02 ± 4.25 mg/mL) and a-glucosidase (IC 50 ¼ 215.51 ± 0.47 mg/mL) activities. Our findings also showed that FeSO 4-induced tissue damage decreased the levels of GSH, SOD, and CAT activities while increasing the levels of MDA. In contrast, treatment with MESFL helped to restore these parameters to near-normal levels, which signifies that MESFL has great potential to address complications from oxidative stress. Furthermore, the in silico interaction of the GCMS-identified phytochemicals with the active sites of a-amylase and a-glucosidase via molecular and ensembled-based docking displayed strong binding affinities of Ar-tumerone and 4-hydroxy-3-methylacetophenone to a-amylase and a-glucosidase, respectively. Taken together, the biological activities of MESFL might be a result of the effects of these secondary metabolites. ARTICLE HISTORY

The present study explores the conformational dynamics of the membrane protein of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) within the Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC) complex using an all-atomistic molecular dynamics simulation approach. Significant structural changes were observed in the N-terminal, C-terminal, transmembrane, and beta-sheet sandwich domains of the MERS-CoV membrane protein. This study also highlights the structural similarities between the MERS-CoV and the SARS-CoV-2 membrane proteins, particularly in how both exhibit a distinct kink in the transmembrane helix caused by aromatic residue-lipid interactions. A structural expansion below the transmembrane and above the beta-sheet sandwich domain within the dimer was observed in all the M-proteins. This site on the beta-sheet sandwich domains near the C-terminal end could serve as a potential drug-binding site. Notably, a stable helical structure was identified in the C-terminal domain of the MERS-CoV membrane protein, whereas a proper secondary structural conformation was not observed in the SARS-CoV-2 membrane protein. Further, the SARS-CoV-2 membrane protein exhibited stronger binding to the lipid bilayer than the MERS-CoV, indicating its greater structural stability within the ERGIC complex. The structural similarity between the membrane protein of MERS-CoV and SARS-CoV-2 suggests the feasibility of employing a common inhibitor against these beta-coronaviruses. Furthermore, this analysis enhances our understanding of the membrane protein’s interactions with proteins and lipids, paving the way for therapeutic developments against these viruses.

In the realm of hospital-acquired and chronic infections, Pseudomonas aeruginosa stands out, demonstrating significant associations with increased morbidity, mortality, and antibiotic resistance. Antibiotic-resistant strains are believed to contribute to thousands of deaths each year. Chronic and latent infections are associated with the bacterial toxin-antitoxin (TA) system, although the mechanisms involved are poorly understood. This study focuses on a novel type II TA system, parDEPa, identified in the genome of P. aeruginosa ATCC 27853. We explored its structural features, functional relationships, and genetic configurations. Our research identified parDEPa homologs in P. aeruginosa, clarified their interactions, and highlighted connections to essential cellular metabolic processes. Notably, homologs of the ParDPa antitoxin were found to be more conserved than the ParEPa toxin. Structural models of the ParEPa toxin and ParDPa antitoxin confirmed their integrity. Through docking and molecular dynamics simulations, we showed that the ParEPa toxin binds to DNA gyrase, inhibiting replication. The stability of the ParDPa-ParEPa complex is primarily driven by hydrophobic interactions (−1763.2 kcal/mol), while the ParEPa-GyrAPa interaction is sustained by strong electrostatic forces (−1294.9 kcal/mol). The RMSD scores indicated greater stability for the ParDPa-ParEPa complex (1.11 Å) than the ParEPa-GyrAPa complex (1.16 Å). RMSF analysis identified key residues involved in the ParDPa-ParEPa complex (Leu59, Gly60, Arg115, Asn116, Arg117) and the ParEPa-GyrAPa complex (Pro48, Gln49, Ser55, Asp94, Gln95). These findings significantly enhance our understanding of the structural and metabolic roles of the chromosomally encoded parDEPa TA module in P. aeruginosa.

Marburg viruses (MARV) are negative-stranded RNA viruses belonging to filoviridae family. This virus causes severe haemorrhagic fever in humans and non-human primates, with a high fatality rate. Currently, there are no vaccines or drugs have been approved to induce productive immunity or control viral infection. As a result, vaccination against this virus is essential for reducing mortality rates. The current study aimed to identify CTL (cytotoxic T lymphocytes) and B-cell epitopes of MARV using in silico tools. A total of 3697 CTL epito-pes and 4577 B-cell epitopes were predicted in the viral proteome of MARV. A reverse vaccinology approach was used to reduce the predicted CTL epitopes by adjusting MHC class I processing, immunogenicity, and other parameters. Finally, epitopes that are non-toxic, antigenic, non-allergenic, and non-homologous to the human proteome were chosen. Among these, 29 novel immunodominant MARV CTL epitopes were docked to their respective HLA alleles and the stability of the interaction was assessed using molecular dynamics simulation. All HLA-epitope complexes were found to be stable indicating that the predicted epitopes are binding with good affinity. Finally, a multi-epitope vaccine with three B-cell epitopes and ten CTL epitopes was designed. The secondary and tertiary structures of the vaccine construct were predicted, refined, and validated. The vaccine construct's codons were then optimized for maximum protein expression. In silico cloning was used to insert the gene construct into the pcDNA 3.1 (þ) vector. This final construct can be used to develop an effective epitope-based MARV vaccine. ARTICLE HISTORY