Streptomyces is the most frequently described genus of Actinomycetes, a producer of biologically active secondary metabolites. Indeed, the Streptomyces species produces about 70% of antibiotics and 60% of antifungal molecules used in agriculture. Our study was carried out with the goal of isolating and identifying antimicrobial secondary metabolites from Streptomyces misionensis V16R3Y1 isolated from the date palm rhizosphere (southern Tunisia). This strain presented a broad range of antifungal activity against Fusarium oxysporum, Aspergillus flavus, Penicillium expansum, Aspergillus niger, Candida albicans, Candida metapsilosis, and Candida parapsilosis and antibacterial activity against human pathogenic bacteria, including Escherichia fergusonii, Staphylococcus aureus, Salmonella enterica, Enterococcus faecalis, Bacillus cereus and Pseudomonas aeruginosa. The purification procedure entailed ethyl acetate extract, silica gel column, and thin layer chromatography. Based on ¹H NMR metabolomic procedure application, also supported by the GC-MS analysis, cyclic dipeptide (l-Leucyl-l-Proline) was identified as the major compound in the bioactive fraction. In order to confirm the identity of the active compound and to have a large quantity thereof, a chemical synthesis of the cyclic dipeptide was performed. The synthetic compound was obtained with a very good yield (50%) and presented almost the same effect compared to the extracted fraction. This study indicates for the first time that Streptomyces misionensis V16R3Y1 exhibits a broad spectrum of antimicrobial activities, produced cyclic dipeptide (l-Leucyl-l-Proline) and might have potential use as a natural agent for pharmaceutical and agri-food applications.

The main objective of this study is to find out the anti-SARS-CoV-2 potential of emetine by using molecular docking and dynamic simulation approaches. Interestingly, molecular docking studies suggest that Emetine showed significant binding affinity toward Nsp15 (-10.8 kcal/mol) followed by Nsp12 (-9.5 kcal/mol), RNA-dependent RNA polymerase, RdRp (-9.5 kcal/mol), Nsp16 (-9.4 kcal/mol), Nsp10 (-9.2 kcal/mol), Papain-like protein (-9.0 kcal/mol), Nsp13 (-9.0 kcal/mol), Nsp14 (-8.9 kcal/mol) and Spike Protein Receptor Domain (-8.8 kcal/mol) and chymotrypsin-like protease, 3CLpro (-8.5 kcal/mol), respectively, which are essential for viral infection and replication. In addition, molecular dynamic simulation (MD) was also performed for 140 ns to explore the stability behavior of the main targets and inhibitor complexes as well as the binding mechanics of the ligand to the target proteins. The obtained MD results followed by absolute binding energy calculation confirm that the binding of emetine at the level of the various receptors is more stable. The complex EmetineNSP15, mechanistically was stabilized as follows: Emetine first binds to the monomer, after, binds to the second inducing the formation of a dimer which in turn leading to the formation of complex that simulation stabilizes it at a value less than 5 Å. Overall, supported by the powerful and good pharmacokinetic data of Emetine, our findings with clinical trials may be helpful to confirm that Emetine could be promoted in the prevention and eradication of COVID-19 by reducing the severity in the infected persons and therefore can open possible new strategies for drug repositioning. Communicated by Ramaswamy H. Sarma

Lobularia maritima, commonly known as sweet alyssum, is an annual ornamental halophyte widely spread along the Tunisian seashore. However, little is known about the phytochemical, antioxidant, and antimicrobial activities of Lobularia maritima. The present study aimed to investigate the potential biological properties of different parts (flowers, leaves, roots, and stems) of Tunisian L. maritima using diverse extraction methods. Extracts were then studied for their antioxidant properties, and the highest antioxidant activity was presented in the roots fractions. Added to this, flower, leaf, and root fractions showed interesting antimicrobial and antifungal activities against different Gram+ and Gram bacteria and against Aspergillus ochraceus. Finally, the most active fractions (presenting the highest biological activities) were analyzed using silica gel purification and mass spectrometry coupled to gas chromatography (GC-MS) analysis, and different compounds were identified such as camphor, amide of oleic acids, tributyl acetylcitrate, betulinaldehyde, menthol, 1-(butyn-3-one-1-yl)-, (1S, 2S, 5R), benzyl benzoate, 7-acetyl-6-ethyl-1,1,4,4-tetramethyltetralin, 2,4-heptadienal, (E,E), and nootkaton-11,12-epoxide. This work represents the first in-depth investigation of the content of bioactive compounds from Lobularia maritima. This species could potentially be a promising source of useful compounds for therapeutic applications.

Metabolic alteration plays a functional role in kidney allograft complications. Metabolomics is a promising high-throughput approach in nephrology but is still limited by the lack of overlap in metabolite coverage. We performed an untargeted fecal metabolomic analysis of forty stable kidney allograft recipients and twenty non-transplant controls. First, we applied the ultra-high performance liquid chromatography (UHPLC) analysis coupled with the Diod Array detector. The potential biomarkers were then collected and identified by gas chromatography-mass spectrometry (GCMS). In order to allow for complete coverage of the fecal polar and non-polar metabolites, the performance of five organic solvents with increasing polarity was investigated successively. UHPLC analysis revealed that the fecal metabolite profiles following the five extractions were significantly different between controls and kidney allografts. GC-MS analysis showed that the best predictors’ metabolites belonged mainly to long-chain fatty acids, phenolic compounds, and amino acids. Collectively, our results showed the efficiency of our pioneer method to successfully discriminate stable kidney-transplant recipients from controls. These findings suggest that distinct metabolic profiles mainly affect fatty acid biosynthesis and amino acid metabolism. In such a context, the novel insights into metabolomic investigation may be a valuable tool that could provide useful new relevant biomarkers for preventing kidney transplant complications.

Recently, beta-carotene has gained tremendous importance as a bioactive molecule due to the growing awareness of the harmful effects of synthetic products. beta-carotene is a high-value natural pigment that has the highest demand in the global carotenoid market owing to its proven antioxidant properties relevant for several diseases. To date, Dunaliella salina is the most important producer of natural beta-carotene and is the subject of important industrial efforts. However, the extraction of beta-carotene remains challenging since all the proposed techniques present a risk of product contamination or loss of quality due to solvent residuals and low yields. The purpose of this study was to set up a green, ecological, and innovative process of extraction of the two major beta-carotene isomers from the halophilic microalgae Dunaliella salina. Based on molecular modeling, docking, and drug design, we conceived and synthesized two chimeric peptides (PP2, PP3) targeting specifically the two major isomers: all-trans or 9-cis beta-carotene. The experimental protocol used in this study demonstrated the ability and the efficacy of those two peptides to cross the cell membrane and bind with high affinity to beta-carotene isomers and exclude them toward the extracellular medium while preserving the integrity of living cells. Interestingly, the tested peptides (PP2, PP3) exhibit significant (f-carotene extraction yields 58% and 34%, respectively, from the total of the beta-carotene in microalgae cells. In addition to its simplicity, this process is fast, independent of the source of the beta-carotene, and selective. These results would allow us to set up a green, ecological, and very profitable process of extraction from microalgae containing high amounts of beta-carotene. Our innovative approach is highly promising for the extraction of Dunaliella salina biomass on an industrial scale.