Membrane-Active Singlet Oxygen Photogenerators as a Paradigm for Broad-Spectrum Antivirals: The Case of Halogenated (BOron)-DIPYrromethenes.

Enveloped viruses, such as flaviviruses and coronaviruses, are pathogens of significant medical concern that cause severe infections in humans. Some photosensitizers are known to possess virucidal activity against enveloped viruses, targeting their lipid bilayer. Here we report a series of halogenated difluoroboron-dipyrromethene (BODIPYs) photosensitizers with strong virus-inactivating activity.

Alkyl Derivatives of Perylene Photosensitizing Antivirals: Towards Understanding the Influence of Lipophilicity.

Amphipathic perylene derivatives are broad-spectrum antivirals against enveloped viruses that act as fusion inhibitors in a light-dependent manner. The compounds target the lipid bilayer of the viral envelope using the lipophilic perylene moiety and photogenerating singlet oxygen, thereby causing damage to unsaturated lipids. Previous studies show that variation of the polar part of the molecule is important for antiviral activity.

Specific Binding of the α-Component of the Lantibiotic Lichenicidin to the Peptidoglycan Precursor Lipid II Predetermines Its Antimicrobial Activity.

To date, a number of lantibiotics have been shown to use lipid II-a highly conserved peptidoglycan precursor in the cytoplasmic membrane of bacteria-as their molecular target. The α-component (Lchα) of the two-component lantibiotic lichenicidin, previously isolated from the VK21 strain, seems to contain two putative lipid II binding sites in its -terminal and -terminal domains. Using NMR spectroscopy in DPC micelles, we obtained convincing evidence that the -terminal mersacidin-like site is involved in the interaction with lipid II.

The Mechanism of Selective Recognition of Lipid Substrate by hDHHC20 Enzyme.

S-acylation is a post-translational linkage of long chain fatty acids to cysteines, playing a key role in normal physiology and disease. In human cells, the reaction is catalyzed by a family of 23 membrane DHHC-acyltransferases (carrying an Asp-His-His-Cys catalytic motif) in two stages: (1) acyl-CoA-mediated autoacylation of the enzyme; and (2) further transfer of the acyl chain to a protein substrate. Despite the availability of a 3D-structure of human acyltransferase (hDHHC20), the molecular aspects of lipid selectivity of DHHC-acyltransferases remain unclear.

Molecular Dynamics of DHHC20 Acyltransferase Suggests Principles of Lipid and Protein Substrate Selectivity.

Lipid modification of viral proteins with fatty acids of different lengths (S-acylation) is crucial for virus pathogenesis. The reaction is catalyzed by members of the DHHC family and proceeds in two steps: the autoacylation is followed by the acyl chain transfer onto protein substrates. The crystal structure of human DHHC20 (hDHHC20), an enzyme involved in the acylation of S-protein of SARS-CoV-2, revealed that the acyl chain may be inserted into a hydrophobic cavity formed by four transmembrane (TM) α-helices.

Structural and Computational Study of the GroEL-Prion Protein Complex.

The molecular chaperone GroEL is designed to promote protein folding and prevent aggregation. However, the interaction between GroEL and the prion protein, PrP, could lead to pathogenic transformation of the latter to the aggregation-prone PrP form. Here, the molecular basis of the interactions in the GroEL-PrP complex is studied with cryo-EM and molecular dynamics approaches.

Molecular Dynamics Insight into the Lipid II Recognition by Type A Lantibiotics: Nisin, Epidermin, and Gallidermin.

Lanthionine-containing peptides (lantibiotics) have been considered as pharmaceutical candidates for decades, although their clinical application has been restricted. Most lantibiotics kill bacteria targeting and segregating of the cell wall precursor-membrane-inserted lipid II molecule-in some cases accompanied by pores formation. Nisin-like lantibiotics specifically bind to pyrophosphate (PPi) moiety of lipid II with their structurally similar N-terminal thioether rings A and B.

Novel cryo-EM structure of an ADP-bound GroEL-GroES complex.

The GroEL-GroES chaperonin complex is a bacterial protein folding system, functioning in an ATP-dependent manner. Upon ATP binding and hydrolysis, it undergoes multiple stages linked to substrate protein binding, folding and release. Structural methods helped to reveal several conformational states and provide more information about the chaperonin functional cycle.

Environmental and dynamic effects explain how nisin captures membrane-bound lipid II.

Antibiotics (AB) resistance is a major threat to global health, thus the development of novel AB classes is urgently needed. Lantibiotics (i.e.

Effects of miniaturization in the anatomy of the minute springtail (Hexapoda: Collembola: Tullbergiidae).

Smaller animals display pecular characteristics related to their small body size, and miniaturization has recently been intensely studied in insects, but not in other arthropods. Collembola, or springtails, are abundant soil microarthropods and form one of the four basal groups of hexapods. Many of them are notably smaller than 1 mm long, which makes them a good model for studying miniaturization effects in arthropods.

[Annexin-5 as a biochemical marker of early vascular disorders under chronic disease of kidneys].

The study evaluated the significance of annexin-5 as a biochemical marker of atherosclerosis in patients with chronic disease of kidneys. The sample consisted of 46 patients with chronic disease of kidneys without clinical symptoms of atherosclerosis. The indicators of lipidogram, intima-media complex of carotid artery reactivity of vessels of microcirculatory channel and concentration of annexin-5 are determined.

[Endothelial dysfunction and apoptosis at early stage of chronic kidney disease].

Aim: To study changes in apoptosis and endothelial function in patients with chronic kidney disease (CKD) stage I-IIIb (CKDsI-IIIb).

Material And Methods: A complex of biochemical, enzyme immunoassay and device investigations was used to examine 128 patients with CKDsI-IIIb.

Results: In CKD stage I reduction of endothelium-dependent vasodilation (EDV) was detected in 34% patients, in stage II -- in 52 %, in stage IIIa -- y 52 %, in stage IIIb - in 70%.

[The level of endothelin-1 and reactivity of skin microvessels in patients with early stages of chronic kidney disease].

Aim: To evaluate endothelin-1 (ET-1) levels and to characterize reflex vasomotor reactions of skin vessels in distant exposure to cold in patients with chronic kidney disease (CKD) of stage I and II.

Material And Methods: Glomerular filtration rate (GFR) was calculated by MDRD formula for 40 healthy subjects (mean age 39.2 +/- 2.

[Heart valve calcification in patients with chronic kidney disease].

The aim of the study was to identify factors related to heart valve calcification (HVC) and effect of HVC on intracardiac hemodynamics in patients with chronic kidney disease (CKD). 377 CKD patients of the control group and 132 ones treated by hemodialysis (HD) were examined using echocardiography, cardiomonitoring, measurement of the carotid intima-media thickness and mineral bone density, X-ray imaging of calcified abdominal aorta. HVC was diagnosed in 38.

[Glomerular filtration rate is an indicator of endothelial function at early stages of chronic kidney disease].

Aim: To study effects of glomerular filtration rate (GFR) reduction on endothelial function in patients at early stages of chronic renal kidney (CKD).

Material And Methods: Endothelial function of 101 patients with CKD of stage I-III was examined using reactive hyperemia test, dopplerography of skin vessels with ionophoresis of acetylcholin and nitroglycerin, lipidogram parameters, homocistein and annexin A5 levels, intima-media complex thickness of the common carotid artery, echocardiography findings.

Results: Cardiovascular complications risk factors were found in all the patients: increased body mass index, arterial hypertension, dyslipoproteinemia, hyperhomocysteinemia.

[Free and conjugated forms of salicylic acid: content and role in potato].

Hydrolysis of conjugated forms of salicylic acid and accumulation of its free form was observed after infection of potato tubers (Solanum tuberosum L.) with an incompatible race of phytophthora or treatment with an elicitor (chitosan). Infection of tubers with a compatible race of the pathogen or treatment with a suppressor (laminarin) decreased both the degree of hydrolysis of conjugated forms of salicylic acid and the accumulation of its free form.

[Effect of systemic signaling molecules on the rate of spread of the immunizing effect of elicitors over potato tissues].

Mobile systemic signaling molecules (salicylic and jasmonic acids) enhance and accelerate the spread of systemic immunizing effect of elicitors (arachidonic acid and chitosan) over potato tuber tissues (Solanum tuberosum L.).

[Regulation of potato immune responses by laminarin].

Laminarin blocks potato immune responses by inhibiting the reaction of oversensitivity, formation of phytoalexins, wound repair, and the activity of proteinase inhibitors. It was found that laminarin exhibits antielicitor activity. Addition of salicylic acid to laminarin enhances its immunosuppressing effect, which becomes systemic.

[Structural-metabolic features of uremic gastroenteropathy].

Concentrations of uremic toxins in the blood and jejunal juice of 72 patients with chronic renal failure (CRF) were studied as well as morphologic changes in biopsies from jejunal mucosa and submucosa, activity and location of acid and alkaline phosphatase as markers of intracellular and transmembrane transport. It was found that maximal excretion of uremic toxins in the jejunum occurs in CRF stage IIA and IIB. In terminal CRF excretion of uremic toxins delays from their concentration in the blood.

[Echotomography in the diagnosis of pleural effusion].

USI of the pleural cavities was performed in 119 patients (65 men and 54 women) aged 30 to 90 with different abnormalities. Pleural fluid in 106 patients was the leading symptom of the main pathological process, in 13 patients it was a sign of pleural disease. USI was combined with routine x-ray methods.