Biosurfactant potential and antiviral activity of multistrain probiotics.

The COVID-19 caused by the SARS-CoV-2 has become a great threat to humans. However, there is no recommendation for an effective and safe drug to treat the disease. The strategy developed in this study is to utilize biosurfactant potential activity of Lactobacillus spp. and Rhodopseudomonas palustris probiotics to prevent the virus from entering human body. The outer membrane of the virus is comprising of phospholipid compounds. Biosurfactants, are known to have detergent-like properties (able to dissolve lipids) that are safe for in vivo use. Thus, the biosurfactant potential activity of the multistrain probiotics extract is expected to be able to disrupt the phospholipid membrane, resulting in the inactivity of the virus to infect human body. The biosurfactant potential activity of the probiotics extract was evaluated using oil spreading, drop collapse, and emulsification methods. The virus infectivity was evaluated on the SARS-CoV-2 of delta variant as a virus model. The results indicated that the probiotics extract has biosurfactant potential activity, able to inhibit virus growth up to 99.9 % within 48 h in the prevention platform, and up to 99.6 % within 48 h in the treatment platform. Therefore, the multistrain probiotics extract was identified to have potential as a promising antiviral agent.

Effect of three LED lights on the biomass production and copper remediation by shoot cultures of Musa paradisiaca.

In photosynthesis, certain wavelengths of radiation are absorbed by photosynthetic pigments in plants, depending on the molecular structures of the pigments. Two main radiation wavelengths absorbed by plants for photosynthesis and biomass production are in the range of red and blue lights. Therefore, in addition to white light, observation applying the red and blue lights in plant researches gain great interest. The aim of this project is to compare the effect of three LED lights on the biomass production and copper remediation by previously-screened shoot cultures of Musa paradisiaca. The LED lights applied are arrangements of white, red, and blue LEDs, each arrangement having the same voltage of 12 V and the same power of 24 Watts. The shoot cultures were cultivated aseptically in 25 mL Murashige and Skoog agar media supplemented with 5 mg/L copper ions. Both parameters -the biomass production and copper concentration in biomass- determine the overall copper remediation by the shoot cultures from media. The results of this project show about 1.5-fold biomass production -expressed as growth index- was obtained upon the application of white light compared to that of the other two lights. Meanwhile, there is no significant difference in the concentration of copper in biomass upon the application of the three lights. Combined together, the application of white light still predominates for the overall copper remediation by the shoot cultures of Musa paradisiaca from media.

Structure-activity relationships for binding of 4-substituted triazole-phenols to macrophage migration inhibitory factor (MIF).

Macrophage migration inhibitory factor (MIF) is a versatile protein that plays a role in inflammation, autoimmune diseases and cancers. Development of novel inhibitors will enable further exploration of MIF as a drug target. In this study, we investigated structure-activity relationships of MIF inhibitors using a MIF tautomerase activity assay to measure binding. Importantly, we notified that transition metals such as copper (II) and zinc (II) interfere with the MIF tautomerase activity under the assay conditions applied. EDTA was added to the assay buffer to avoid interference of residual heavy metals with tautomerase activity measurements. Using these assay conditions the structure-activity relationships for MIF binding of a series of triazole-phenols was explored. The most potent inhibitors in this series provided activities in the low micromolar range. Enzyme kinetic analysis indicates competitive binding that proved reversible. Binding to the enzyme was confirmed using a microscale thermophoresis (MST) assay. Molecular modelling was used to rationalize the observed structure-activity relationships. The most potent inhibitor 2d inhibited proliferation of A549 cells in a clonogenic assay. In addition, 2d attenuated MIF induced ERK phosphorylation in A549 cells. Altogether, this study provides insights in the structure-activity relationships for MIF binding of triazole-phenols and further validates this class of compounds as MIF binding agents in cell-based studies.

Small-molecule inhibitors of macrophage migration inhibitory factor (MIF) as an emerging class of therapeutics for immune disorders.

Macrophage migration inhibitory factor (MIF) is an important cytokine for which an increasing number of functions is being described in the pathogenesis of inflammation and cancer. Nevertheless, the availability of potent and druglike MIF inhibitors that are well-characterized in relevant disease models remains limited. Development of highly potent and selective small-molecule MIF inhibitors and validation of their use in relevant disease models will advance drug discovery. In this review, we provide an overview of recent advances in the identification of MIF as a pharmacological target in the pathogenesis of inflammatory diseases and cancer. We also give an overview of the current developments in the discovery and design of small-molecule MIF inhibitors and define future aims in this field.

High yield production of human invariant chain CD74 constructs fused to solubility-enhancing peptides and characterization of their MIF-binding capacities.

The HLA class II histocompatibility antigen gamma chain, also known as HLA-DR antigen-associated invariant chain or CD74, has been shown to be involved in many biological processes amongst which antigen loading and transport of MHC class II molecules from the endoplasmic reticulum to the Golgi complex. It is also part of a receptor complex for macrophage migration inhibitory factor (MIF), and participates in inflammatory signaling. The inhibition of MIF-CD74 complex formation is regarded as a potentially attractive therapeutic target in inflammation, cancer and immune diseases. In order to be able to produce large quantities of the extracellular moiety of human CD74, which has been reported to be unstable and protease-sensitive, different constructs were made as fusions with two solubility enhancers: the well-known maltose-binding domain and Fh8, a small protein secreted by the parasite Fasciola hepatica. The fusion proteins could be purified with high yields from Escherichia coli and were demonstrated to be active in binding to MIF. Moreover, our results strongly suggest that the MIF binding site is located in the sequence between the transmembrane and the membrane-distal trimerisation domain of CD74, and comprises at least amino acids 113-125 of CD74.

Discovery of chromenes as inhibitors of macrophage migration inhibitory factor.

Macrophage migration inhibitory factor (MIF) is an essential signaling cytokine with a key role in the immune system. Binding of MIF to its molecular targets such as, among others, the cluster of differentiation 74 (CD74) receptor plays a key role in inflammatory diseases and cancer. Therefore, the identification of MIF binding compounds gained importance in drug discovery. In this study, we aimed to discover novel MIF binding compounds by screening of a focused compound collection for inhibition of its tautomerase enzyme activity. Inspired by the known chromen-4-one inhibitor Orita-13, a focused collection of compounds with a chromene scaffold was screened for MIF binding. The library was synthesized using versatile cyanoacetamide chemistry to provide diversely substituted chromenes. The screening provided inhibitors with IC50's in the low micromolar range. Kinetic evaluation suggested that the inhibitors were reversible and did not bind in the binding pocket of the substrate. Thus, we discovered novel inhibitors of the MIF tautomerase activity, which may ultimately support the development of novel therapeutic agents against diseases in which MIF is involved.