Iskanje po katalogu digitalne knjižnice

Opis: Furin cleavage of the SARS-CoV-2 spike protein results in a polybasic terminal sequence termed the C-end rule (CendR), which is responsible for the binding to neuropilin 1 (NRP1), enhancing viral infectivity and entry into the cell. Here we report the identification of 20 small-molecule inhibitors that emerged from a virtual screening of nearly 950,000 drug-like compounds that bind with high probability to the CendR-binding pocket of NRP1. In a spike NRP1 binding assay, two of these compounds displayed a stronger inhibition of spike protein binding to NRP1 than the known NRP1 antagonist EG00229, for which the inhibition of the CendR peptide binding to NRP1 was also experimentally confirmed. These compounds present a good starting point for the design of small-molecule antagonists against the SARS-CoV-2 viral entry.
Ključne besede: neuropilin 1, SARS-CoV-2, COVID-19, spike binding inhibitors, virtual screening, small-molecule antagonists, molecular docking, in vitro binding assay
Objavljeno v DKUM: 09.05.2025; Ogledov: 0; Prenosov: 0
Celotno besedilo (6,27 MB)
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Opis: Rosemary (Rosmarinus officinalis L.) represents a medicinal plant known for its various health-promoting properties. Its extracts and essential oils exhibit antioxidative, anti-inflammatory, anticarcinogenic, and antimicrobial activities. The main compounds responsible for these effects are the diterpenes carnosic acid, carnosol, and rosmanol, as well as the phenolic acid ester rosmarinic acid. However, surprisingly little is known about the molecular mechanisms responsible for the pharmacological activities of rosemary and its compounds. To discern these mechanisms, we performed a large-scale inverse molecular docking study to identify their potential protein targets. Listed compounds were separately docked into predicted binding sites of all non-redundant holo proteins from the Protein Data Bank and those with the top scores were further examined. We focused on proteins directly related to human health, including human and mammalian proteins as well as proteins from pathogenic bacteria, viruses, and parasites. The observed interactions of rosemary compounds indeed confirm the beforementioned activities, whereas we also identified their potential for anticoagulant and antiparasitic actions. The obtained results were carefully checked against the existing experimental findings from the scientific literature as well as further validated using both redocking procedures and retrospective metrics.
Ključne besede: rosemary, inverse molecular docking, carnosol, carnosic acid, rosmanol, rosmarinic acid
Objavljeno v DKUM: 10.04.2025; Ogledov: 0; Prenosov: 2
Celotno besedilo (65,93 MB)
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Opis: Since December 2019, the new SARS-CoV-2-related COVID-19 disease has caused a global pandemic and shut down the public life worldwide. Several proteins have emerged as potential therapeutic targets for drug development, and we sought out to review the commercially available and marketed SARS-CoV-2-targeted libraries ready for high-throughput virtual screening (HTVS). We evaluated the SARS-CoV-2-targeted, protease-inhibitor-focused and protein–protein-interactioninhibitor-focused libraries to gain a better understanding of how these libraries were designed. The most common were ligand- and structure-based approaches, along with various filtering steps, using molecular descriptors. Often, these methods were combined to obtain the final library. We recognized the abundance of targeted libraries offered and complimented by the inclusion of analytical data; however, serious concerns had to be raised. Namely, vendors lack the information on the library design and the references to the primary literature. Few references to active compounds were also provided when using the ligand-based design and usually only protein classes or a general panel of targets were listed, along with a general reference to the methods, such as molecular docking for the structure-based design. No receptor data, docking protocols or even references to the applied molecular docking software (or other HTVS software), and no pharmacophore or filter design details were given. No detailed functional group or chemical space analyses were reported, and no specific orientation of the libraries toward the design of covalent or noncovalent inhibitors could be observed. All libraries contained pan-assay interference compounds (PAINS), rapid elimination of swill compounds (REOS) and aggregators, as well as focused on the drug-like model, with the majority of compounds possessing their molecular mass around 500 g/mol. These facts do not bode well for the use of the reviewed libraries in drug design and lend themselves to commercial drug companies to focus on and improve.
Ključne besede: targeted libraries, focused libraries, computer-aided drug design, virtual screening, in silico drug design, high-throughput virtual screening
Objavljeno v DKUM: 09.04.2025; Ogledov: 0; Prenosov: 3
Celotno besedilo (6,53 MB)
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Opis: Nanomaterials and sensors play an important role in modern technologies, including medical diagnostics and biochemical research. This work presents the possibility of using o-Phthaldialdehyde (OPA) in combination with 3-mercaptopropyltriethoxysilane (MPTES) to develop a dopamine-responsive sensor. During the experiment, these materials were used at different pH and ratios to determine the optimal parameters for obtaining high fluorescence intensity of the reaction product. The data obtained demonstrate a linear relationship between the fluorescence response (λex/λem = 340/460 nm) of OPA/MPTES and dopamine concentration in the range of 0.1–3.0 µM at a pH of 8, and the detection limit was 8.7 nM. The obtained results confirm the potential of OPA/MPTES as a sensing component for the detection of dopamine
Ključne besede: fluorometric method, dopamine, o-phthalaldehyde
Objavljeno v DKUM: 13.03.2025; Ogledov: 0; Prenosov: 1
Celotno besedilo (3,17 MB)

Ključne besede: oscillatory reactions, Bray–Liebhafsky reaction, benzenediols, chemical sensors, radical scavenging
Objavljeno v DKUM: 31.01.2025; Ogledov: 0; Prenosov: 3
Celotno besedilo (4,69 MB)