Methicillin-Resistant Staphylococcus aureus (MRSA), a pathogenic bacterium that causes life-threatening outbreaks such as community-onset and nosocomial infections as emerging ‘superbug’. Time and motion study of its virulent property developed resistance against most of the antibiotics such as Vancomycin. Thereby, to curb this problem entails the development of new therapeutic agents. Plant-derived antimicrobial agents have recently piqued people's interest, so in this research, 186 flavonoids compound selected to unmask the best candidates that can act as potent inhibitors against the Penicillin Binding Protein-2a (PBP-2a) of MRSA. Molecular docking performed using PyRx and GOLD suite to determine the binding affinities and interactions between the phytochemicals and the PBP-2a. The selected candidates strongly interact with the different amino acid residues. The 30 ns molecular dynamics (MD) simulations with five top-ranked compounds such as Naringin, Hesperidin, Neohesperidin, Didymin and Icariin validated the docking interactions. These findings are also strongly supported by root-mean-square deviation, root-mean-square fluctuation and the radius of gyration. ADME/T analysis demonstrates that these candidates appear to be safer inhibitors. Our findings point to natural flavonoids as a promising and readily available source of adjuvant antimicrobial therapy against resistant strains in the future. Communicated by Ramaswamy H. Sarma

COVID-19’s ongoing, protracted visitation has prevented due acknowledgement of efforts to control it, particularly those of the medical workers who volunteered to serve on the frontlines, disregarding uncertainty and personal risk, in the early days when the consequences of exposure were unknown. This artwork seeks to memorialise the diligence, selflessness, and professional commitment of the medical community in a time of extraordinary difficulty. Referencing historical patterns of iconography, this graphic imagery proposes a modernised representation of bravery by interweaving narratives of equality, inclusivity, humour and optimism, to recognise the unnamed many who helped make the world a safer place.

SGK1 (Serum and Glucocorticoid Regulated Kinase 1), a serine/threonine kinase that is activated by various stimuli, including serum and glucocorticoids. It controls inflammation, apoptosis, hormone release, neuro-excitability and cell proliferation, all of which play an important role in cancer progression and metastasis. SGK1 was recently proposed as a potential drug target for cancer, diabetes, and neurodegenerative diseases. In this study, molecular docking, physiochemical, toxicological properties and molecular dynamic simulation of the Bis-[1-N,7-N, Pyrazolo tetraethoxyphthalimido{-4-(3,5-Dimethyl-4-(spiro-3-methylpyazolo)-1,7-dihydro-1H-dipyrazolo[3,4-b;4',3'-e]pyridin-8-yl)}]p-disubstituted phenyl compoundsand reference EMD638683 against new SGK1 target protein. Compared to the reference inhibitor EMD638683, we choose the best compounds (series 2-6) based on the binding energy (in the range from −11.0 to −10.6 kcal/mol). With the exception of compounds 2 and 6, none of the compounds posed a risk for AMES toxicity or carcinogenicity due to their toxicological properties. 100 ns MD simulation accompanied by MM/PBSA energy calculations and PCA. According to MD simulation results, the binding of compounds 3, 4 and 5 stabilizes the SGK1 structure and causes febrile conformational changes compared to EMD638683. As a result of this research, the final selected compounds 3, 4 and 5 can be used as scaffolds to develop promising SGK1 inhibitors for the treatment of related diseases such as cancer. Graphical Abstract Communicated by Ramaswamy H. Sarma

Triple-negative breast cancer (TNBC) is the most aggressive among the breast cancer subtypes and poses unique therapeutic challenges due to its distinct characteristics like lack of specific therapeutic targets. TNBC demonstrates poor survival rate enhanced immunogenic characteristics and a more favorable tumor microenvironment than other breast cancer variants. Also, TNBC patients show elevated levels of programmed death ligand-1 (PD-L1) expression in contrast to non-TNBC patients. Binding of PD-L1 with PD-1 produces an inhibitory signal, resulting in suppression of T-cell. Therapeutic approaches utilizing immunotherapies against PD-L1 exhibit promising outcomes in the treatment of TNBC. Limitations like suboptimal efficacy, inadequate oral bioavailability, and associated immune-related adverse effects of antibody-mediated anti PD-1/PD-L1 therapies have necessitated the exploration of alternative therapeutic approaches. Thus, small molecules become an alternate option for PD-1/PD-L1 inhibition. In the present study, we have used virtual screening to identify potential phytochemicals from selected Indian medicinal plants as PD-L1 inhibitors. A total of 953 phytochemicals derived from eleven selected medicinal plants were initially screened through molecular docking using the PyRx tool. Among the 953 identified phytochemicals, the top 20 compounds exhibiting the highest binding affinities in docking study were selected for further analysis. Following comprehensive ADMET analyses, 2 compounds were ultimately identified as suitable candidates for a molecular dynamics (MD) simulation study. The study identified 4-hydroxychalcone and flavylium from Glycyrrhiza glabra and Catharanthus roseus, respectively as potential PD-L1 inhibitors with enhanced stability relative to the reference molecule. Both compounds also showed enhanced gastrointestinal absorption with no predicted cytotoxic and immunotoxic effects. Consequently, these compounds present promising candidates for novel PD-L1 inhibitor development in TNBC therapy. Further experimental investigations are necessary to facilitate their clinical translation.

Due to poorly managed diabetes, diabetic foot ulcers (DFUs) often have elevated MMP-9 levels that slow wound healing. High levels of matrix metalloproteinases (MMPs), notably MMP-9, which are necessary for inflammation and wound repair, slow DFU recovery. This study investigates phytocompounds from Ocimum sanctum as MMP-9 inhibitors for diabetic foot ulcers to promote wound healing and develop effective treatments. Phytocompounds from Ocimum sanctum were compared to (R)-ND-336 for MMP-9 inhibition via molecular docking. Toxicology, ADME, and drug-likeness were assessed. MMP-9 interactions and compound stability were analyzed by molecular dynamics simulations, whereas reactivity was tested using density functional theory calculations. The binding stability was determined using structural and energetic studies. Docking experiments discovered nine phytochemicals with higher binding affinities than (R)-ND-336. Seven compounds met Lipinski’s rule of five and demonstrated drug-like properties. Cytotoxicity, hepatotoxicity, and neurotoxicity were absent in most substances, while chlorogenic acid and rosmarinic acid showed immunotoxicity. Docking research revealed strong binding affinities between MMP-9 and cianidanol, luteolin, rosmarinic acid, apigenin, and quercetin (-9.1 to -9.8 kcal/mol). Thermal study demonstrated spontaneous binding of rosmarinic acid and quercetin. In HOMO-LUMO analysis, smaller energy gaps suggested greater reactivity and metabolic stability. Molecular electrostatic potential research showed lutein was most polar. Molecular dynamics simulations validated apigenin’s stability, negligible RMSD variations, optimal SASA, and robust receptor binding. This study investigates apigenin, a phytochemical found in Ocimum sanctum, as a prospective inhibitor of MMP-9 for the healing of diabetic foot ulcers.

Liver cancer is one of the deadliest cancers worldwide. There is a growing need for natural therapeutic options due to the rising global morbidity incidence of liver cancer. Due to its crucial function in angiogenesis, vascular endothelial growth factor (VEGF) signaling is considered as an ideal target for therapeutic intervention. In this in silico study, we have screened 16 microRNAs (miRNAs) that target the KDR gene, which encode VEGFR-2, and 113 natural compounds derived from Persicaria hydropiper for their anti-angiogenic properties. MicroRNA, hsa-miR-17-3p was identified with potentials of downregulating KDR gene, using several in silico tools. Two possible compounds- 6-Hydroxyluteolin and Isorhamnetin were also identified after performing ADMET profiling and molecular docking. Furthermore, 100 ns molecular dynamics simulations were run to evaluate the stability and conformational changes of protein-ligand complexes. This study identified one microRNA and two natural compounds that showed strong interaction with KDR and its encoded VEGFR-2 receptor, respectively. To validate their effectiveness as therapeutic agents against hepatocellular carcinoma, additional wet lab studies using in vitro and in vivo techniques are necessary.