In Vitro Activity of Beauvericin against All Developmental Stages of Sarcoptes scabiei.

Scabies is a frequent cutaneous infection caused by the mite Sarcoptes scabiei in a large number of mammals, including humans. As the resistance of S. scabiei against several chemical acaricides has been previously documented, the establishment of alternative and effective control molecules is required. In this study, the potential acaricidal activity of beauvericin was assessed against different life stages of S. scabiei var. suis and in comparison with dimpylate and ivermectin, two commercially available molecules used for the treatment of S. scabiei infection in animals and/or humans. The toxicity of beauvericin against cultured human fibroblast skin cells was evaluated using an MTT proliferation assay. In our in vitro model, developmental stages of S. scabiei were placed in petri dishes filled with Columbia agar supplemented with pig serum and different concentrations of the drugs. Cell sensitivity assays demonstrated low toxicity of beauvericin against primary human fibroblast skin cells. At 0.5 and 5 mM, beauvericin showed higher activity against adults and eggs of S. scabiei compared to dimpylate and ivermectin. These results revealed that the use of beauvericin is promising and might be considered for the treatment of S. scabiei infection.

Computational Applications: Beauvericin from a Mycotoxin into a Humanized Drug.

Drug discovery was initially attributed to coincidence or experimental research. Historically, the traditional approaches were complex, lengthy, and expensive, entailing costly random screening of synthesized compounds or natural products coupled with in vivo validation largely depending on the availability of appropriate animal models. Currently, in silico modeling has become a vital tool for drug discovery and repurposing. Molecular docking and dynamic simulations are being used to find the best match between a ligand and a molecule, an approach that could help predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana, being originally studied for its potential use as a pesticide. BEA is now considered a molecule of interest for its possible use in diverse biotechnological applications in the pharmaceutical industry and medicine. In this manuscript, we provide an overview of the repurposing of BEA as a potential therapeutic agent for multiple diseases. Furthermore, considerable emphasis is given to the fundamental role of in silico techniques to (i) further investigate the activity spectrum of BEA, a secondary metabolite, and (ii) elucidate its mode of action.

In silico evidence of beauvericin antiviral activity against SARS-CoV-2.

BACKGROUND: Scientists are still battling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus 2019 (COVID-19) pandemic so human lives can be saved worldwide. Secondary fungal metabolites are of intense interest due to their broad range of pharmaceutical properties. Beauvericin (BEA) is a secondary metabolite produced by the fungus Beauveria bassiana. Although promising anti-viral activity has previously been reported for BEA, studies investigating its therapeutic potential are limited. METHODS: The objective of this study was to assess the potential usage of BEA as an anti-viral molecule via protein-protein docking approaches using MolSoft. RESULTS: In-silico results revealed relatively favorable binding energies for BEA to different viral proteins implicated in the vital life stages of this virus. Of particular interest is the capability of BEA to dock to both the main coronavirus protease (Pockets A and B) and spike proteins. These results were validated by molecular dynamic simulation (Gromacs). Several parameters, such as root-mean-square deviation/fluctuation, the radius of gyration, H-bonding, and free binding energy were analyzed. Computational analyses revealed that interaction of BEA with the main protease pockets in addition to the spike glycoprotein remained stable. CONCLUSION: Altogether, our results suggest that BEA might be considered as a potential competitive and allosteric agonist inhibitor with therapeutic options for treating COVID-19 pending in vitro and in vivo validation.

Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods.

Multi-drug resistance is posing major challenges in suppressing the population of pests. Many herbivores develop resistance, causing a prolonged survival after exposure to a previously effective pesticide. Consequently, resistant pests reduce the yield of agricultural production, causing significant economic losses and reducing food security. Therefore, overpowering resistance acquisition of crop pests is a must. The ATP binding cassette transporters (ABC transporters) are considered as the main participants to the pesticide efflux and their neutralization will greatly contribute to potentiate failed treatments. Real-Time PCR analysis of 19 ABC transporter genes belonging to the ABCB, ABCC, ABCG, and ABCH revealed that a broad range of efflux pumps is activated in response to the exposure to pesticides. In this study, we used beauvericin (BEA), a known ABC transporters modulator, to resensitize different strains of Tetranychus urticae after artificial selection for resistance to cyflumetofen, bifenazate, and abamectin. Our results showed that the combinatorial treatment of pesticide (manufacturer's recommended doses) + BEA (sublethal doses: 0.15 mg/L) significantly suppressed the resistant populations of T. urticae when compared to single-drug treatments. Moreover, after selective pressure for 40 generations, the LC50 values were significantly reduced from 36.5, 44.7, and 94.5 (pesticide) to 8.3, 12.5, and 23.4 (pesticide + BEA) for cyflumetofen, bifenazate, and abamectin, respectively. While the downstream targets for BEA are still elusive, we demonstrated hereby that it synergizes with sub-lethal doses of different pesticides and increases their effect by inhibiting ABC transporters. This is the first report to document such combinatorial activity of BEA against higher invertebrates paving the way for its usage in treating refractory cases of resistance to pesticides. Moreover, we demonstrated, for the first time, using in silico techniques, the higher affinity of BEA to ABC transformers subfamilies when compared to xenobiotics; thus, elucidating the pathway of the mycotoxin.

First evidence of the activity of an entomopathogenic fungus against the eggs of Sarcoptes scabiei.

The entomopathogenic fungus Beauveria bassiana has been successfully used for the control of phytopathogenic arthropods and there are a growing number of studies suggesting that this kind of fungus could also be used for the control of ectoparasites in mammals. This study evaluated for the first time the efficacy of different Beauveria strains against the eggs of Sarcoptes scabiei collected from experimentally infected pigs. Eggs were exposed to fungal conidia and monitored for hatching over 10 days. The strongest effect (28.75 % of hatching inhibition) was obtained with a commercial B. bassiana strain. Furthermore, the detection of fungal genomic within the surface-cleaned eggs demonstrated the ability of B. bassiana to penetrate and proliferate in the egg-shell of S. scabiei. This study provides the first evidence, using molecular techniques, that the development of mycoacaricides may be of interest for the control of S. scabiei infection.

The bees of Lebanon (Hymenoptera: Apoidea: Anthophila).

The study of wild bees has markedly increased in recent years due to their importance as pollinators of crops and wild plants, and this interest has been accentuated by increasing evidence of global declines in their abundance and species richness. Though best studied in Europe and North America, knowledge on the current state of wild bees is scarce in regions where they are particularly diversified, such as the Mediterranean basin. The eastern Mediterranean country of Lebanon, located at the heart of the Levant in a biodiversity hotspot, is particularly poorly studied. The aim of this paper is to produce a first annotated checklist of the wild bees of Lebanon from new and museum collections, literature records, and verified occurrences from online databases. The present list totals 573 species for Lebanon of which 289 are reported for the first time, but the estimated diversity is likely to be closer to 700. Preliminary information on local distributions and flower records are also presented. The local species assemblages indicate affinities with montane habitats of the Mediterranean and Anatolia and the semi-arid habitats of the Levant and north Africa. This study also encourages further research on local wild bee faunas and the use of this knowledge for conservation purposes.

Bioexploration and Phylogenetic Placement of Entomopathogenic Fungi of the Genus Beauveria in Soils of Lebanon Cedar Forests.

The cedar forests of Lebanon have been threatened by the outbreak caused by climate change of a web-spinning sawfly, Cephalcia tannourinensis (Hymenoptera: Pamphiliidae), which negatively impacted the survival of one of the oldest tree species on earth. In this study, we investigated the occurrence of naturally soil-inhabiting entomopathogenic fungi for their role in containing the massive outbreak of this insect. We used a combination of fungal bioexploration methods, including insect bait and selective media. Morphological features and multilocus phylogeny-based on Sanger sequencing of the transcripts encoding the translation elongation factor 1-alpha (TEF-α), RNA polymerase II second largest subunit (RBP2), and the nuclear intergenic region (Bloc) were used for species identification. The occurrence rate of entomopathogenic fungi (EPF) varied with location, soil structure, forest structure, and isolation method. From 15 soil samples positive for fungal occurrence, a total of 249 isolates was obtained from all locations using different isolation methods. The phylogenetic analysis confirmed the existence of two novel indigenous species: Beauveria tannourinensis sp. nov. and Beauveria ehdenensis sp. nov. In conclusion, the present survey was successful (1) in optimizing the isolation methods for EPF, (2) investigating the natural occurrence of Beauveria spp. in outbreak areas of C. tannourinensis, and (3) in characterizing the presence of new Beauveria species in Lebanese cedar forest soil.