Development, production and characterization of SARS-CoV-2 virus-like particles (Coronaviridae: Orthocoronavirinae: Betacoronavirus: Sarbecovirus).

INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 has created serious health problems worldwide. The most effective way to prevent the occurrence of new epidemic outbreaks is vaccination. One of the modern and effective approaches to vaccine development is the use of virus-like particles (VLPs). The aim of the study is to develop a technology for production of VLP based on recombinant SARS-CoV-2 proteins (E, M, N and S) in insect cells. MATERIALS AND METHODS: Synthetic genes encoding coronavirus proteins E, M, N and S were used. VLP with various surface proteins of strains similar to the Wuhan virus, Delta, Alpha and Omicron were developed and cloned into the pFastBac plasmid. The proteins were synthesized in the baculovirus expression system and assembled into VLP in the portable Trichoplusia ni cell. The presence of insertion in the baculovirus genome was determined by PCR. ELISA and immunoblotting were used to study the antigenic activity of VLP. VLP purification was performed by ultracentrifugation using 20% sucrose. Morphology was assessed using electron microscopy and dynamic light scattering. RESULTS: VLPs consisting of recombinant SARS-CoV-2 proteins (S, M, E and N) were obtained and characterized. The specific binding of antigenic determinants in synthesized VLPs with antibodies to SARS-CoV-2 proteins has been demonstrated. The immunogenic properties of VLPs have been studied. CONCLUSION: The production and purification of recombinant VLPs consisting of full-length SARS-CoV-2 proteins with a universal set of surface antigens have been developed and optimized. Self-assembling particles that mimic the coronavirus virion induce a specific immune response against SARS-CoV-2.

[Antiviral properties of synthetic histidine derivatives containing membranotropic volumetrical carbocycles in their molecule against SARS-CoV-2 virus in vitro].

INTRODUCTION: Currently, low molecular-weight compounds are being developed as potential inhibitors of CoVs replication, targeting various stages of the replication cycle, such as major protease inhibitors and nucleoside analogs. Viroporins can be alternative protein targets. The aim of this study is to identify antiviral properties of histidine derivatives with cage substituents in relation to pandemic strain SARS-CoV-2 in vitro. MATERIALS AND METHODS: Combination of histidine with aminoadamantane and boron cluster anion [B10H10]2 (compounds IIV) was carried out by classical peptide synthesis. Compound were identified by modern physicochemical methods. Antiviral properties were studied in vitro on a monolayer of Vero E6 cells infected with SARS-CoV-2 (alpha strain) with simultaneous administration of compounds and virus. RESULTS: Derivatives of amino acid histidine with carbocycles and boron cluster were synthesized and their antiviral activity against SARS-CoV-2 was studied in vitro. Histidine derivatives with carbocycles and [B10H10]2 have the ability to suppress virus replication. The solubility of substances in aqueous media can be increased due to formation of hydrochloride or sodium salt. DISCUSSION: 2HCl*H-His-Rim (I) showed some effect of suppressing replication of SARS-CoV-2 at a viral load of 100 doses and concentration 31.2 g/ml. This is explained by the weakly basic properties of compound I. CONCLUSION: The presented synthetic compounds showed moderate antiviral activity against SARS-CoV-2. The obtained compounds can be used as model structures for creating new direct-acting drugs against modern strains of coronaviruses.

[Pathobiomechanical impairments of the vertebral column in intervertebral disk protrusion and herniation].

Magnetic resonance imaging of patients with intervertebral disk herniation was used to study the stages of degenerative and dystrophic processes in the spinal structures in the presence of intervertebral disk protrusion and herniation. Differences were found in the pathobiomechanical mechanisms in the spinal motor segments of herniation and protrusion in the area of their localization and in the adjacent spinal motor segments. Among the symptoms traditionally analyzed, joint facet joint arthritis and arthrosoarthritis classified as spondyloarthritis by radiodiagnosis were examined for their impact on the rate of herniation and protrusion.

Effect of imipramine on the behavior and cerebral 5-HT1A serotonin receptors in mice genetically predisposed to catalepsy.

Acute injection of imipramine to NPK mice hereditary predisposed to pinching catalepsy reduced immobility in the forced swimming test, but had no effect on catalepsy. Chronic treatment with imipramine reduced the severity of catalepsy and functional activity of 5-HT1A serotonin receptors, but did not modify their expression in the hippocampus. NPK mice can be a convenient model for studies of the effects of antidepressant.

[A multicenter evaluation of efficacy and tolerance in the local treatment with dolgit cream of patients with osteoarthrosis]. / Mnogotsentrovaia otsena éffektivnosti i perenosimosti lokal'noi terapii kremom dolgit u bol'nykh osteoartrozom.

A 2-week clinical trial of cream dolgit efficacy and tolerance in 76 patients with primary osteoarthritis in 8 rheumatological centers showed this preparation to reduce local pain syndrome in 70.1%, palpation pain sensitivity in 79.2%, joint swelling in 75.5% of patients. Unwanted reactions in the form of skin itch at the site of application were reported in 7.8% of cases.

[The characteristics of a Russian-made kit for the serological identification of streptococci groups A, B and C]. / Kharakteristika otechestvennogo nabora dlia serologicheskoi identifikatsii streptokokkov grupp A, B, C.

The first Soviet kits for the serological identification of streptococci, groups A, B, and C, on the basis of the coagglutination test were developed. Each kit was intended for 35-40 determinations. The optimum concentration of streptococci during their identification by means of the reagents making up the kit was about 1.6 x 10(9) cells/ml. The specificity of the reagents in comparison with the results of the identification of streptococci by reference methods was 97.3 +/- 0.9%. The reagents making up the kits can be presumably used for solving a number of practical problems in the epidemiological surveillance of streptococcal infection.