Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate
Viral mRNA cap methyltransferases (MTases) are emerging targets for the development of broad-spectrum antiviral agents. In this work, we designed potential SARS-CoV-2 MTase Nsp14 and Nsp16 inhibitors by using bioisosteric substitution of the sulfonium and amino acid substructures of the cosubstrate S-adenosylmethionine (SAM), which serves as the methyl donor in the enzymatic reaction. The synthetically accessible target structures were prioritized using molecular docking. Testing of the inhibitory activity of the synthesized compounds showed nanomolar to submicromolar IC50 values for five compounds. To evaluate selectivity, enzymatic inhibition of the human glycine N-methyltransferase invol…
In vitro impact preliminary assessment of airborne particulate from metalworking and woodworking industries.
Abstract BackgroundInhalation is the main route of exposure to airborne pollutants. To evaluate the safety and assess the risks of occupational hazards different testing approaches are used. 3D airway epithelial tissues allow to mimic exposure conditions in vitro, generates human-relevant toxicology data, allows to elucidate mode of action of pollutants. ResultsGilian 3500 pumps equipped with Standard Midget Impingers were used to collect the airborne particulate from woodworking and metalworking environments. EpiAirway™ tissues were used to model half working day (4 h), full working day (8 h), and 3 working day exposures to occupational pollutants. Tissue viability was assessed using MTT a…
Anti-Bacterial Activity and Online HPLC-DPPH Based Antiradical Kinetics of Medicinal Plant Extracts of High Relevance for Cosmetics Production
The present study provides an assessment of extracts of six medicinal plants for their applicability in cosmetic formulations aimed at anti-UV protection and anti-acne treatment. Ethanol extracts of Chelidonium majus L., Myrtus communis L., Hamamelis virginiana L., Juniperus communis L., Alchemilla vulgaris and Ilex paraguariensis are analysed for the phytochemical content, antimicrobial activity, antiradical activity and antiradical kinetics. The phytochemical composition of the plants is investigated by LC-MS analysis and the most active antioxidants in plant extracts are determined by online HPLC-DPPH assay. The kinetic parameters of the antiradical reaction are determined both for the s…
Effect of crosslinking strategy on the biological, antibacterial and physicochemical performance of hyaluronic acid and ɛ-polylysine based hydrogels
The design of multifunctional hydrogels based on bioactive hyaluronic acid (HA) and antibacterial cationic polymer ε-poly-L-lysine (ε-PL) is a promising tool in tissue engineering applications. In the current study, we have designed hyaluronic acid and ε-polylysine composite hydrogel systems with antibacterial and cell attractive properties. Two distinct crosslinking approaches were used: the physical crosslinking based on electrostatic at- tractions and the chemical crosslinking of charged functional groups (-NH2 and -COOH). The impact of the crosslinking strategy on fabricated hydrogel molecular structure, swelling behavior, gel fraction, morphology, porosity, visc…
Effect of the oncolytic ECHO-7 virus Rigvir® on the viability of cell lines of human origin in vitro
Background: The role of oncolytic viruses in cancer treatment is increasingly studied. The first oncolytic virus (Rigvir®, ECHO-7) was registered in Latvia over a decade ago. In a recent retrospective study Rigvir® decreased mortality 4.39-6.57-fold in stage IB-IIC melanoma patients. The aims of the present study are to test the effect of Rigvir® on cell line viability in vitro and to visualize the cellular presence of Rigvir® by immunocytochemistry. Methods: The cytolytic effect of Rigvir® on the viability of FM-9, RD, AGS, A549, HDFa, HPAF‑II, MSC, MCF7, HaCaT, and Sk-Mel-28 cell lines was measured using live cell imaging. PBMC viability was measured using flow cytometry. The presence of …
Cultivation of 3D Dermal Tissue by Application of Autologous Matrix
Abstract The most common reasons for major skin loss are thermal trauma — burns and scalds that can result in rapid, extensive, deep wounds as well as chronic non-healing wounds. Treatment using common techniques is poor and depending on the trauma level can result in death. There is a substantial need for skin integrity restoration. The main goal of this study was to develop an autologous 3D skin model that could eventually be translated into clinical applications. The study examined a variety of factors — extracellular matrix components, cell count, culture medium modification and role of structurally and functionally high-quality 3D skin dermis layer tissue culture production. The result…
Evaluation of dermal toxicity of antibacterial cotton textile coated by sol-gel technology
AbstractThis paper reports about cotton textile modification by sol-gel technology with the purpose of obtaining antibacterial properties, evaluation of antibacterial properties and dermal toxicity tests of cotton textile with Zn and Si coating. Antibacterial properties evaluation against pathogenic microorganisms Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli made using the Parallel streak method in accordance with ATCC147 standard. For more specific evaluation of the coated textile, in vitro cytotoxicity test with epidermal HaCat cells was done. It is concluded that the coatings containing Zn and Si obtained by the sol-gel technology can impart antibacterial propertie…