[The effect of etiopathogenetic therapy of COVID-19 on the severity of the disease: results of a multicenter double-blind placebo-controlled randomized trial].

AIM: The search for etiopathogenetic agents to prevent the development of severe and extremely severe COVID-19 remains relevant. A placebo-controlled randomized clinical trial was conducted to evaluate the efficacy and safety of the antibody-based biological drug (Raphamin). MATERIALS AND METHODS: 785 outpatients 18-75 y.o. with laboratory confirmed mild COVID-19 were included within 24 hours from the disease onset. 771 patients were randomized to the group Raphamin (n=382) and the Placebo group (n=389). The study drug/placebo was prescribed for 5 days. The rate of progression to a more severe degree of COVID-19 by day 28 as well as the time to sustained clinical recovery and the frequency of hospitalization were evaluated. Safety was assessed taking into account adverse events, vital signs and laboratory parameters. RESULTS: The number of cases of progression to a more severe degree of COVID-19 in participants receiving Raphamin was 59 (15.5%) [52 (14.6%)] versus placebo - 89 (22.9%) [85 (23.7%)], ITT and [PP] analysis data are presented. The odds ratio between groups was OR=0.6157 [OR=0.5494], 95% confidence interval 0.4276-0.8866 [0.3750-0.8048], which meant a reduction in the chance of progression to a more severe degree by 38.4% [45.1%] or 1.48 [1.62] times; p=0.0088 [p=0.0019]. The time to sustained recovery in the Raphamin group was 4.5±2.4 [4.6±2.4] days, versus placebo - 5.8±4.7 [6.0±4.8] days; p=0.0025 [p=0.0036]. No adverse events with a certain relationship were registered. CONCLUSION: Raphamin reduces the risk of progression to a more severe degree of the COVID-19 and significantly shortens the duration of clinical symptoms.

[Evaluation of the efficacy and safety of a complex antiviral drug based on antibodies in the treatment of adult patients with acute respiratory viral infection].

AIM: To evaluate the efficacy and safety of Raphamin, containing technologically processed affinity-purified antibodies to interferon , CD4 receptor, 1 domain of the major histocompatibility complex class II and 2 microglobulin major histocompatibility complex class I in the treatment of acute respiratory viral infection (ARVI), including influenza, in adults. MATERIALS AND METHODS: 240 patients 1870 years old with ARVI were included in a phase III (20192020), randomized, double-blind, placebo-controlled trial. Pregnant women, patients with suspected bacterial infections were excluded from the study. Raphamin/placebo was prescribed for 5 days within 24 hours of the illness onset. Primary endpoint was a time to resolution of ARVI (Polymerase chain reaction PCR-confirmed). Additionally, the severity of ARVI, proportion of patients with ARVI resolution/worsening/complications, frequency of antipyretics prescription, and time to resolution of symptoms of ARVI (including PCR non confirmed) were assessed. RESULTS: The average time to resolution of ARVI (PCR-confirmed) was 4.11.9 [4.01.9] and 5.02.5 [5.02.5] days in the Raphamin/placebo groups (ITT and [PP] analysis, р=0.0155 and [р=0.0114], respectively). The duration of ARVI decreased by 0.892.23 [0.932.25] days. Superiority of Raphamin was shown during therapy period according to the ARVI resolution criterion (р=0.0014 [р=0.0005]). There were no statistically significant difference in the severity of ARVI and frequency of antipyretics prescription. The proportion of patients with worsening/complications was 0 [0]% and 2.5 [2.8]% in the Raphamin and placebo groups, respectively. Favorable safety profile of Raphamin (including the incidence and severity of adverse events) and high compliance were shown. CONCLUSION: Raphamin promotes significant decrease, practically by a day, the duration of ARVI, including influenza.

[Comparison of different ELISAs for detection of antibodies to swine vesicular disease virus in sera from experimentally infected animals].

The study has shown the efficiency of a competitive ELISA (C-ELISA) variant or an indirect ELISA (I-ELUSA) in the detection of antibodies to swine vesicular disease virus (SVDV) versus traditional assays, such as a microneutralization test, a blocking ELIDA test, and a the reference test Ceditest SVDV (Cedi-Diagnostics B.V., Netherlands). Specific antibodies in the pig sera could be detected by C-ELISA on days 4-5 and by I-ELISA on day 6 after experimental SVDV infection. Specific antibodies were detected in a contact pig 11 days after the beginning of the experiment.

[Use of blue-green algae for biogas production].

Perspectives for nature protection and energy-saving, by using blue-green algae, are discussed. Utilization of their phyto biomass for biogas manufacture will lead to the environmental normalization of the Transdniestria and allow one to have about 19,000,000 m3 of methane only from the water area of only one Kremenchug water basin each vegetative period (70 days).

Site-specific endonuclease AbaI from Azospirillum brasilense UQ 1796 is an isoschizomer of endonuclease BclI.

The site-specific endonuclease AbaI was isolated and purified to functional purity from the soil nitrogen-fixing bacterium Azospirillum brasilense UQ 1796. Purification included successive chromatography on columns with phosphocellulose, heparin-Sepharose, and hydroxyapatite. The purified enzyme recognizes the palindromic DNA sequence 5'-T decreases ATCA-3' and cleaves it as shown by the arrow. The isolated enzyme belongs to class II restriction endonuclease and is an isoschizomer of endonuclease BclI. The enzyme of AbaI is active at 26-56 degrees C. The optimal temperature is 48 degrees C and the optimal buffer is LRB.

[Isolation of DNA-membrane complexes from Bacillus subtilis]. / Uydelenie i sostav DNK-membrannykh kompleksov iz Bacillus subtilis.

The DNA-membrane complexes were isolated from the membranes of Bacillus subtilis, disrupted by ultrasonication and subjected to chromatography on Sepharose 4B. The membrane-bound fraction of native 3H-DNA was found only in the freshly isolated material. The phospholipid and protein composition of this fraction was determined. It was assumed that the newly synthesized membrane-associated 3H-DNA from Bacillus subtilis is bound to the lipoprotein complexes enriched with phospholipids.

[Effects of polyene antibiotics and detergents on cell membranes of polyene-sensitive and polyene-resistant strains of Candida albicans]. / Deistbie Polienovykh antibiotikov i detergentov na kletochnye membrany chuvstvitel'nogo i rezistentnogo k polienam shtammov Candida albicans.

Various detergents and EPR-probes of 4,4-dimethylspiro[5alpha-androstan-17beta-ol-3,2-(1,3-oxazolidin-3-oxyl)]2CH3OH; 2,2,6,6-tetramethylpalmitoyl-amidopiperidine-1-oxyl and 2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinoxyl were used to establish structural differences in the membrane of polyene-sensitive and polyene-resistant strains of C. albicans. It was shown that the type of protein-lipid interactions is modified by the changes in the sterol component of the polyene-resistant strain membranes. This manifests itself in a decrease in sensitivity of membrane alkaline phosphatase for levorin and the detergents, as well as in the alteration of the lipid fluidity pattern of the polyene-resistant strain membranes as compared to the membranes of original culture of C. albicans. Treatment of polyene-sensitive strain membranes with amphotericine B causes more intensive protein-lipid interactions, which is not observed in case of the polyene-resistant strain. It is assumed that C. albicans resistance to polyenes is due to the existence of strong protein-lipid interactions in the membrane coupled with ergosterol substitution by other sterol components.

[Membranes of bacteria and mechanism of action of the antibiotic gramicidin S]. / Membrany bakterii i mekhanizm deistviia antibiotika gramitsidina S

The cyclopeptide antibiotic gramicidin S taken at a concentration of 100--200 mkg/mg membrane protein rapidly increases the permeability of M. lysodeikticus protoplast membranes for substrates of respiratory chain and exogenous cytochromes c. Prolonged incubation of gramicidin S with protoplasts results in their lysis which is more fast at low temperatures. In contrast to natural gramicidin, a derivative of gramicidin S with acetylated amino groups does not inhibit either the micrococcus membrane dehydrogenase or the whole of respiratory chain and does not affect the osmotic barrier of protoplasts. Aliphatic diamines (at concentrations up to 0.1 M) and Ca2+ ions (10(-2) M) do not affect the functioning of the respiratory chain in isolated micrococcus membranes. Another derivative of the antibiotic with an increased distance of loaded amino groups from the cyclopeptide framework (diglycyl gramicidin S) affects the membrane in a way similar to that of natural gramicidin. Washing of gramicidin-treated membranes with NaCl enhances the inhibitory effect of the antibiotic on membrane enzymes. The data obtained suggest that in addition to ionic interactions some hydrophobic interactions also occur during gramicidin S binding to the bacterial membrane, probably at the expense of a hydrophobic peptide ring. It is assumed that gramicidin S, similar to Ca2+ and some other membranotropic agents provides for phase separation of negatively charged phospholipids from other groups of phospholipids, manifesting itself in an appearance of "frozen" sites on the membrane which destroys its barrier properties. This is due to the formation of ionic bonds of negatively charged phospholipids. Simultaneously, unlike Ca2+, gramicidin S, when interacting with membrane proteins, prevents their redistribution in more liquid parts of the membrane, which results in a situation when the respiratory enzymes become surrounded by alkyl chains with restricted motion.