Biology subjects

Ebrahimi, B.

Publications and source records attributed to Ebrahimi, B..

4 recordsLinked to original sources

bioRxiv2026

The potent anti-influenza virus activity of FluPep is mediated by interactions with cellular anionic polysaccharides

FluPep is a 16 amino-acid peptide with potent anti-viral activity against influenza A virus, including the H1N1 subtype. To understand how FluPep exerts its effects, gold nanoparticles were functionalised with FluPep, since gold nanoparticles provide a very sensitive probe that can be detected optically. Our results demonstrate that nanoparticle-FluPep conjugates did not bind to influenza virus particles in vitro. However, the nanoparticle-FluPep conjugates bound to polyanions on the cell surface, and after washing cells they remained cell-associated and were able to inhibit flu virus infectivity. Nanoparticle-FluPep conjugates bound to heparin affinity columns and their binding to cells could be reduced by pre-treatment of the cells with heparinase and neuraminidase, but not with chondroitinase ABC. These data indicated that FluPep bound to heparan sulfate and sialic acid-containing glycans in the pericellular matrix and in doing so prevented viral infectivity. The importance of the interaction of FluPep with heparan sulfate (HS) was examined by extending FluPep at its C-terminus with amino acid sequences responsible for the interactions of growth factors with heparin. The resultant two new engineered peptides, termed superFluPep1 and superFluPep2, were more potent than parental FluPep. The results demonstrate that FluPep likely exerts its antiviral activity by interfering with virus-cell interactions and that enhancing the binding of such peptides to heparan sulfate is an effective strategy to increase their anti viral potency.

biochemistry↗

bioRxiv2023

Odor-evoked transcriptomics of Aedes aegypti mosquitoes

Modulation of odorant receptors mRNA induced by prolonged odor exposure is highly correlated with ligand-receptor interactions in Drosophila as well as mammals of the Muridae family. If this response feature is conserved in other organisms, this presents a potentially potent initial screening tool when searching for novel receptor-ligand interactions in species with predominantly orphan olfactory receptors. We demonstrate that mRNA modulation in response to 1-octen-3-ol odor exposure occurs in a time- and concentration-dependent manner in Aedes aegypti mosquitoes. To investigate gene expression patterns at a global level, we generated an odor-evoked transcriptome associated with 1-octen-3-ol odor exposure. Transcriptomic data revealed that ORs and OBPs were transcriptionally responsive whereas other chemosensory gene families showed little to no differential expression. Alongside chemosensory gene expression changes, transcriptomic analysis found that prolonged exposure to 1-octen-3-ol modulated xenobiotic response genes, primarily members of the cytochrome P450, insect cuticle proteins, and glucuronosyltransferases families. Together, these findings suggest that mRNA transcriptional modulation caused by prolonged odor exposure is pervasive across taxa and accompanied by the activation of xenobiotic responses. Furthermore, odor-evoked transcriptomics create a potential screening tool for filtering and identification of chemosensory and xenobiotic targets of interest.

neuroscience↗

bioRxiv2020

Novel Three-Dimensional Organoid Sarcoidosis Granuloma Model

Sarcoidosis is a multi-system disorder of granulomatous inflammation which most commonly affects the lungs. Its etiology and pathogenesis are not well defined in part due to the lack of reliable modeling. This article presents the development of a novel in vitro three-dimensional lung-on-chip organoid designed to mimic granuloma formation. A lung on chip fluidic macrodevice with three channels for cell culture insertion was developed and added to the previously developed a lung-on-membrane model. Granulomas were cultured from blood samples of patients with sarcoidosis and then inserted in the air-lung-interface (ALI) of the microchip to create a three-dimensional organoid sarcoidosis model (OSGM). The model was tested for cell viability with fibroblasts. We measured the cytokine profiles in medium of OSGM and compared with lung model without granuloma. Concentration of IL-1beta, Il-6, GM-CSF, and IFN-gamma were found significantly higher in OSGM group. The current model represents the first 3D OSGM created by adding a microfluidics system to a dual-chambered lung on membrane model and introducing developed sarcoid-granuloma to its ALI.

immunology↗

bioRxiv2018

Enhanced inhibition of influenza virus infection by peptide-noble metal nanoparticle conjugates

Influenza virus is a major medical and veterinary health concern and causes global pandemics. The peptide FluPep is an established inhibitor of influenza virus infectivity in model systems. We have explored the potential for FluPep functionalised noble metal nanoparticle to enhance the antiviral activity of the peptide Flupep and determined their potential for the delivery of FluPep. The FluPep ligand designed here is FluPep extended at its N-terminus with the sequence CVVVTAAA-, to allow its incorporation into a mix matrix ligand shell of a peptidol and an alkanethiol ethyleneglycol comprising 70% H-CVVVTol and 30% HS(CH2)11(ethyleneglycol)4 (both mole/mole). Gold and silver nanoparticles (~10 nm diameter) prepared with up to 5% (mole/mole) FluPep ligand contained in the mixture of mix-matrix peptide ligands remained as stable as the control mix-matrix coated nanoparticles against ligand exchange with dithiothreitol. FluPep ligand was found to inhibit viral plaque formation in canine MDCK cells (IC50 2.1 nM), but was less potent than FluPep itself (IC50 140 pM). FluPep ligand functonalised nanoparticles retained antiviral activity in the plaque assay. Moreover, at low grafting densities (where nanoparticles incorporate ~1 FluPep ligand, the antiviral potency in terms of FluPep ligand concentration was enhanced significantly for gold and silver nanoparticles (IC50 ~8-fold and ~3-fold lower, respectively). At higher grafting density the potency relative to free FluPep ligand concentration decreased. The data demonstrate that conjugation of FluPep to gold and silver nanoparticles enhances its antiviral potency; the antimicrobial activity of silver ions may enable the design of even more potent anti-microbial inhibitors.

biochemistry↗