Impact of mutations on the stability of SARS-CoV-2 nucleocapsid protein structure.

The nucleocapsid (N) protein of SARS-CoV-2 is known to participate in various host cellular processes, including interferon inhibition, RNA interference, apoptosis, and regulation of virus life cycles. Additionally, it has potential as a diagnostic antigen and/or immunogen. Our research focuses on examining structural changes caused by mutations in the N protein.

Design of new chemical entities targeting both native and H275Y mutant influenza a virus by deep reinforcement learning.

Influenza virus remains a major public health challenge due to its high morbidity and mortality and seasonal surge. Although antiviral drugs against the influenza virus are widely used as a first-line defense, the virus undergoes rapid genetic changes, resulting in the emergence of drug-resistant strains. Thus, new antiviral drugs that can outwit resistant strains are of significant importance.

Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery.

Human carbonic anhydrase XII (hCA XII) isozyme is of high therapeutic value as a pharmacological target and biomarker for different types of cancer. The hCA XII is one of the crucial effectors that regulates extracellular and intracellular pH and affects cancer cell proliferation, invasion, growth and metastasis. Despite the fact that interaction features of hCAs inhibitors with the catalytic site of the enzyme are well described, lack in the selectivity of the traditional hCA inhibitors based on the sulfonamide group or related motifs is an urgent issue.

A new microtubule-stabilizing agent shows potent antiviral effects against African swine fever virus with no cytotoxicity.

African swine fever virus (ASFV) is the causal agent of a fatal disease of domestic swine for which no effective antiviral drugs are available. Recently, it has been shown that microtubule-targeting agents hamper the infection cycle of different viruses. In this study, we conducted in silico screening against the colchicine binding site (CBS) of tubulin and found three new compounds with anti-ASFV activity.

In silico study of colchicine resistance molecular mechanisms caused by tubulin structural polymorphism.

Starting from 1972, colchicine is known as the most useful drug for prevention of familial Mediterranean fever attacks. However, some patients do not respond to colchicine treatment, even taken in high doses. Despite the fact, that different hypotheses have been proposed, the molecular mechanisms of colchicine resistance are not completely clear.

[In silico Search for Tubulin Polymerization Inhibitors].

Cytostatic colchicine is widely used in the treatment of Familial Mediterranean fever, but it has several side effects. For finding new, more effective drugs with higher affinity and diminishside effects we carried out virtual screening of potential inhibitors of the main target of colchicine, the polymerization of tubulin by evaluating affinity 25745 compounds, structurally related to the colchicine. We have identified 11 commercially available compounds with higher affinity to tubulin.

Genistein inhibits African swine fever virus replication in vitro by disrupting viral DNA synthesis.

African swine fever virus (ASFV) is the causal agent of a highly-contagious and fatal disease of domestic pigs, leading to serious socio-economic consequences in affected countries. Once, neither an anti-viral drug nor an effective vaccines are available, studies on new anti-ASFV molecules are urgently need. Recently, it has been shown that ASFV type II topoisomerase (ASFV-topo II) is inhibited by several fluoroquinolones (bacterial DNA topoisomerase inhibitors), raising the idea that this viral enzyme can be a potential target for drug development against ASFV.

Complex formation dynamics of native and mutated pyrin's B30.2 domain with caspase-1.

Pyrin protein is the product of the MEFV gene, mutations in which cause manifestation of familial Mediterranean fever (FMF). Functions of pyrin are not completely clear. The secondary structure of the pyrin is represented with four domains and two motifs.

Brief Report: Association of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome With Gonosomal Mosaicism of a Novel 24-Nucleotide TNFRSF1A Deletion.

Objective: To investigate the molecular cause of persistent fevers in a patient returning from working overseas, in whom investigations for tropical diseases yielded negative results.

Methods: DNA was extracted from the patient's whole blood, leukocyte subpopulations, saliva, hair root, and sperm. The TNFRSF1A gene was analyzed by polymerase chain reaction (PCR), allele-specific PCR, Sanger sequencing, and next-generation sequencing.

[Influence of M680I and M694V mutations on pyrin's domain B30.2 tertiary structure and it's complex formation ability with caspase-1].

The M680I and M694V mutations located in the B30.2 pyrin domain are responsible for the manifestation of the most common forms of Familial Mediterranean fever. It is well known that a malfunction of the pyrin-caspase-1 complex is the main cause of inflammation in FMF.

Mono- and polysynaptic connections between identified neurons in the system of the passive avoidance reflex of the snail.

The structure of the synaptic connections between identified sensory and giant command neurons of the parietal ganglia of the snail is examined. It is shown that the excitatory postsynaptic potential arising in the giant neuron in response to the generation of a single action potential in the presynaptic neuron consists of several monosynaptic components and may include polysynaptic components. It is hypothesized that monosynaptic components of the elementary excitatory postsynaptic potential that differ in the duration of the latent period and the dynamics of habituation may be associated with the activation of synaptic buttons on axon terminals of varying length.

The vision of the snail: the spectral sensitivity of the dark-adapted eye.

The spectral sensitivity of the dark-adapted eye of the snail Helix lucorum L. was investigated in semi-intact "optic cupoptic nerve-cerebral ganglion" preparations. The data of the recording of the electroretinogram in response to monochromatic radiation of varied intensities were used to plot the spectral sensitivity functions.

[Vision in the snail: the morphology and electrical activity of the optic nerve].

Light stimulation of a snail's eye elicits spikes in the optic nerve with the latency less by 150-170 ms than that of a corresponding retinal ERG-reaction. This period is constant independently of the intensity of stimulus. Sensory part of the optic nerve consists of at least three types of fibres defining action potentials with different amplitudes and thresholds.

[The mono- and polysynaptic connections between identified neurons in the system of the passive defensive reflex in the edible snail].

A structure of synaptic connections between the identified sensory and giant command neurons of Helix lucorum was studied. It was found that EPSPs arising in the giant neuron as responses to single action potentials generation in sensory neuron consist of several monosynaptic and several polysynaptic components having different magnitude, latencies, and plasticity. The latencies of monosynaptic components are determined by different presynaptic terminals' lengths.

[Vision in the edible snail: the spectral sensitivity of the dark-adapted eye].

The spectral sensitivity of the dark-adapted eye of Helix lucorum L. was investigated using a semi-intact preparation "ball of the eye--optic nerve--cerebral ganglion". The amplitudes of responses of the electroretinogram to monochromatic stimuli of different intensities were used for a reconstruction of the spectral sensitivity.

[Vision in the edible snail. The morphology and total electrical activity of the retina].

Recording of the integrative electrical activity of the retina of the snail and electron microscopic study of its eye have shown the following. The electrical activity of the photoreceptors is a source of the retinogram (ERG) of the snail. ERG reaction form is characterized by two phases of a response: the initial spike and the following slow fading.

The monosynaptic connection: modulating influence of opioid peptides on the plasticity of presynaptic neurons and identified synapses.

An investigation of the effect of opioid peptides (leucine-enkephalin and methionine-enkephalin) on the plastic properties of the system of monosynaptically connected LPa7-LPa3 and RPa3, and LPa8-LPa3 and RPa3, neurons in the brain of the edible snail was carried out. It was demonstrated that all three elements in the system under investigation (the presynaptic neuron, the postsynaptic neuron, and the synapse) display the same type of plasticity, i.e.

[The monosynaptic connection: the modulating effect of opioid peptides on the plasticity of presynaptic neurons and identified synapses].

Study of opioid peptides (leucine-enkephalin and methionine-enkephalin) action on plastic properties of the system of monosynaptically connected neurones LPa7--LPa3, PPa3 and LPa8--LPa3, PPa3 was conducted in the snail brain. It has been shown that all three links in the system studied (presynaptic neurone, postsynaptic neurone and synapse) manifest one and the same type of plasticity--habituation to rhythmic stimulation. Enkephalins have a modulating action on plastic properties of the presynaptic neurone and synapse: they retard the habituation of the presynaptic neurone to intracellular stimulation and retard the development of habituation at synaptic level.

Monosynaptic connection: identifiable synapses in the CNS of the edible snail.

The microanatomy of the pre- and postsynaptic neurons and the structure of the monosynaptic connection LPa7-LPa3 are described on the basis of planar reconstruction of sections of preparations of the CNS of the edible snail with neurons marked by heavy metal salts. Some physiological features of the presynaptic neuron and the monosynaptic connection were studied. The criteria for the identification of the LPa7 neuron according to its position in the ganglion, to the physiological reaction of LPa3, and to its microanatomy were determined.

[The monosynaptic connection: identified synapses in the CNS of the edible snail].

By electrophysiological and microanatomical methods of analysis of snail CNS small neurones it was shown that a number of neurones form a monosynaptic connection (MSC) with the gigantic polyfunctional neurone LPa3. By using cobalt and nickel staining, the structure of MSC cells LPa7--LPa3 was studied. Six identified synapses in two LPa3 processes zones were found.