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WHO declared severe acute respiratory syndrome coronavirus-2' (SARS-CoV-2) was global health emergency since 2020. In our study eighteen natural compounds were investigated for possible anti–SARS-CoV-2 potential, where the most potent natural compounds were ursolic acid and dioscin with IC50 value of 4.49 µg/mL and 7.11 µg/mL, respectively. Hesperidin, catechin, diosmin, isorhamnetin-3-O-glucoside and hyperoside showed medium antiviral activity with IC50 value of 20.87, 22.57, 38.92, 39.62 and 47.10 µg/mL, respectively. Molecular modelling studies including docking study and predictive ADME study were performed on all tested molecules. Their binding energies after docking were calculated and their orientations at the active sites of both SARS-CoV-2 main protease (Mpro) and spike (S) receptors were visualised and compared to the downloaded ligands. Also, the predictive ADME studies showed good pharmacokinetic properties of most of the tested compounds. The obtained in silico results obtained confirmed that many of the tested compounds are promising SARS-CoV-2 inhibitors. [ABSTRACT FROM AUTHOR]

Summary: Antibiotic resistance is now deemed a worldwide problem that puts public health at risk. The potential of Murraya (Murraya koenigii (L.) Spreng. and Murraya paniculata (L.) Jacq.) leaves and stems as antibacterial agents against multidrug‐resistant Acinetobacter baumannii (MDRAB) was assessed in our study. First, screening was performed by disc diffusion assay, and minimum inhibitory concentration values were then determined as compared to tigecycline. A. baumnii mouse model of infection was established to substantiate the antibacterial activity of Murraya species. Results revealed high antimicrobial activity for stem of both plants where leaves showed moderate to weak activity. Phytochemical characterisation revealed the identification of 129 metabolites belonging to different classes of compounds viz. coumarins, carbazole alkaloids, flavonoids, phenolic acids, and miscellaneous. In vivo data from the animal model supported the high efficiency of M. paniculata stems as promising extract for lead candidates against MDRAB pulmonary infections. Inhibition of its essential MurF (UDP‐N‐acetylmuramoyl‐tripeptide‐D‐alanyl‐d‐alanine ligase) protein has been reported as a potential target for broad‐spectrum drugs. In silico results after molecular docking to MurF from Acinetobacter baumannii (PDB ID: 4QF5) showed competitive binding mode to ATP ligand at the active site predicting antibacterial activity of the tested compounds. Furthermore, chlorogenic acid, caffeic acid, sinapic acid, feruloyl agmatine, and mahanimbidine were detected as the key discriminatory metabolites correlated with antibacterial activity. To our knowledge, this is the first in vivo anti‐MDRAB study for the investigated plant. Murraya plants have enormous possibility for the discovery of novel bioactive compounds which could combat against resistant microorganisms. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial‐resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin‐resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin's anti‐Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano‐gold emulsion, and curcumin nanoemulsion. Methods: The antimicrobial activities of the investigated compounds, both individually and in combination with other anti‐Helicobacter drugs, were evaluated. Their antibiofilm and anti‐virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis. Results: We observed high anti‐Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti‐biofilm and anti‐virulence compound among the examined substances. The biofilm‐correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post‐treatment with curcumin nanoemulsion. On the protein level, the anti‐virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination. Conclusion: The anti‐Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub‐MIC levels could enhance the anti‐Helicobacter activity of azithromycin and exhibit anti‐virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment. [ABSTRACT FROM AUTHOR]