Pharmacokinetic and preclinical safety studies of endolysin-based therapeutic for intravenous administration.

Pharmacokinetics and safety studies of innovative drugs is an essential part of drug development process. Previously we have developed a novel drug for intravenous administration (lyophilizate) containing modified endolysin LysECD7-SMAP that showed notable antibacterial effect in different animal models of systemic infections. Here we present data on pharmacokinetics of endolysin in mice after single and multiple injections.

Pharmacokinetics and Preclinical Safety Studies of Modified Endolysin-based Gel for Topical Application.

Antibacterial therapy with phage-encoded endolysins or their modified derivatives with improved antibacterial, biochemical and pharmacokinetic properties is one of the most promising strategies that can supply existing antibacterial drugs array. Gram-negative bacteria-induced infections treatment is especially challenging because of rapidly spreading bacterial resistance. We have developed modified endolysin LysECD7-SMAP with a significant antibacterial activity and broad spectra of action against gram-negative bacteria.

Biofilm-disrupting effects of phage endolysins LysAm24, LysAp22, LysECD7, and LysSi3: breakdown the matrix.

The ability of most opportunistic bacteria to form biofilms, coupled with antimicrobial resistance, hinder the efforts to control widespread infections, resulting in high risks of negative outcomes and economic costs. Endolysins are promising compounds that efficiently combat bacteria, including multidrug-resistant strains and biofilms, without a low probability of subsequent emergence of stable endolysin-resistant phenotypes. However, the details of antibiofilm effects of these enzymes are poorly understood.

New conjugates based on N4-hydroxycytidine with more potent antiviral efficacy in vitro than EIDD-2801 against SARS-CoV-2 and other human coronaviruses.

The spread of COVID-19 continues due to genetic variation in SARS-CoV-2. Highly mutated variants of SARS-CoV-2 have an increased transmissibility and immune evasion. Due to the emergence of various new variants of the virus, there is an urgent need to develop broadly effective specific drugs for therapeutic strategies for the prevention and treatment of COVID-19.

Alginate Gel Encapsulated with Enzybiotics Cocktail Is Effective against Multispecies Biofilms.

The development of new and effective antibacterials for pharmaceutical or cosmetic skin care that have a low potential for the emergence and expansion of bacterial resistance is of high demand in scientific and applied research. Great hopes are placed on alternative agents such as bactericidal peptidoglycan hydrolases, depolymerases, etc. Enzybiotic-based preparations are being studied for the treatment of various infections and, among others, can be used as topical formulations and dressings with protein-polysaccharide complexes.

Estimation of anti-orthopoxvirus immunity in Moscow residents and potential risks of spreading Monkeypox virus.

WHO has declared the outbreak of monkeypox as a public health emergency of international concern. In less than three months, monkeypox was detected in more than 30 000 people and spread to more than 80 countries around the world. It is believed that the immunity formed to smallpox vaccine can protect from monkeypox infection with high efficiency.

Antiviral Activity of N,N-Disubstituted Uracil Derivatives against SARS-CoV-2 Variants of Concern.

Despite the widespread use of the COVID-19 vaccines, the search for effective antiviral drugs for the treatment of patients infected with SARS-CoV-2 is still relevant. Genetic variability leads to the continued circulation of new variants of concern (VOC). There is a significant decrease in the effectiveness of antibody-based therapy, which raises concerns about the development of new antiviral drugs with a high spectrum of activity against VOCs.

Sputnik V Effectiveness against Hospitalization with COVID-19 during Omicron Dominance.

Mass vaccination campaigns against COVID-19 affected more than 90% of the population in most developed countries. The new epidemiologic wave of COVID-19 has been ongoing since the end of 2021. It is caused by a virus variant B.

Label-Free Detection of the Receptor-Binding Domain of the SARS-CoV-2 Spike Glycoprotein at Physiologically Relevant Concentrations Using Surface-Enhanced Raman Spectroscopy.

Surface-enhanced Raman scattering (SERS) spectroscopy is a surface- or cavity-enhanced variant of Raman scattering spectroscopy that allows the detection of analytes with a sensitivity down to single molecules. This method involves the use of SERS-active surfaces or cavities capable of concentrating incident radiation into small mode volumes containing the analyte. Here, we have engineered an ultranarrow metal-dielectric nano-cavity out of a film of the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) glycoprotein and a silver surface, held together by interaction between reduced protein sulfhydryl groups and silver.

Microbiological Characteristics of Some Stations of Moscow Subway.

The subway is one of the most actively used means of transport in the traffic infrastructure of large metropolitan areas. More than seven million passengers use the Moscow subway every day, which promotes the exchange of microorganisms between people and the surrounding subway environment. In this research, a study of the bacterial communities of two Moscow subway stations was conducted and the common subway microbiome was determined.

A Strategy for the Rapid Development of a Safe Candidate Vaccine Strain.

Approximately 1/6 of humanity is at high risk of experiencing cholera epidemics. The development of effective and safe vaccines against the primary cause of cholera, is part of the public health measures to prevent cholera epidemics. Natural nontoxigenic isolates represent a source of new genetically improved and relatively safe vaccine strains.

Discovering the Potentials of Four Phage Endolysins to Combat Gram-Negative Infections.

Endolysin-based therapeutics are promising antibacterial agents and can successfully supplement the existing antibacterial drugs array. It is specifically important in the case of Gram-negative pathogens, e.g.

Efficacy of the Endolysin-Based Antibacterial Gel for Treatment of Anaerobic Infection Caused by .

Abscess formation is a common complication of severe life-threatening infections caused by obligate anaerobes. is among the frequently detected anaerobic pathogens from clinical specimens associated with liver abscesses, skin and soft tissue infections, or oral abscesses. The antimicrobial therapy for this kind of infection needs to be optimized.

Contamination of Hospital Surfaces with Bacterial Pathogens under the Current COVID-19 Outbreak.

The SARS-CoV-2 pandemic remains a global health issue for several reasons, such as the low vaccination rates and a lack of developed herd immunity to the evolution of SARS-CoV-2, as well as its potential inclination to elude neutralizing antibodies. It should be noted that the severity of the COVID-19 disease is significantly affected by the presence of co-infections. Comorbid conditions are caused not only by pathogenic and opportunistic microorganisms but also by some representatives of the environmental microbiome.

Relation between lignin molecular profile and fungal exo-proteome during kraft lignin modification by Trametes hirsuta LE-BIN 072.

The process of kraft lignin modification by the white-rot fungus Trametes hirsuta was investigated using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS), and groups of systematically changing compounds were delineated. In the course of cultivation, fungus tended to degrade progressively more reduced compounds and produced more oxidized ones. However, this process was not gradual - the substantial discontinuity was observed between 6th and 10th days of cultivation.

Safety and Immunogenicity of the GamTBvac, the Recombinant Subunit Tuberculosis Vaccine Candidate: A Phase II, Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study.

GamTBvac is a candidate tuberculosis vaccine with two fusion proteins, containing Ag85a, ESAT6, CFP10, and a dextran-binding domain (DBD). Phase II of a double-blind, randomized, multicenter, placebo-controlled study in parallel groups in healthy adults to evaluate the safety and immunogenicity of GamTBvac in 180 previously-vaccinated with Bacillus Calmette-Guérin vaccine (BCG) healthy volunteers without (MTB) infection was conducted. The dose (0.

Resistance to peptidoglycan-degrading enzymes.

The spread of bacterial strains resistant to commonly used antibiotics urges the development of novel antibacterial compounds. Ideally, these novel antimicrobials should be less prone to the development of resistance. Peptidoglycan-degrading enzymes are a promising class of compounds with a fundamentally different mode of action compared to traditionally used antibiotics.

Antibiofilm Activity of a Broad-Range Recombinant Endolysin LysECD7: In Vitro and In Vivo Study.

Surfaces of implanted medical devices are highly susceptible to biofilm formation. Bacteria in biofilms are embedded in a self-produced extracellular matrix that inhibits the penetration of antibiotics and significantly contributes to the mechanical stability of the colonizing community which leads to an increase in morbidity and mortality rate in clinical settings. Therefore, new antibiofilm approaches and substances are urgently needed.

Modulation of Endolysin LysECD7 Bactericidal Activity by Different Peptide Tag Fusion.

The use of recombinant endolysins is a promising approach for antimicrobial therapy capable of counteracting the spread of antibiotic-resistant strains. To obtain the necessary biotechnological product, diverse peptide tags are often fused to the endolysin sequence to simplify enzyme purification, improve its ability to permeabilize the bacterial outer membrane, etc. We compared the effects of two different types of protein modifications on endolysin LysECD7 bactericidal activity in vitro and demonstrated that it is significantly modulated by specific permeabilizing antimicrobial peptides, as well as by widely used histidine tags.

Fungal Adaptation to the Advanced Stages of Wood Decomposition: Insights from the .

is a white rot basidiomycete with wide ecological amplitude. It occurs in different regions of Russia and throughout the world, occupying different climatic zones. colonizes stumps, trunks, and branches of various deciduous (seldom coniferous) trees.

First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment.

Tuberculosis is known to be the biggest global health problem, causing the most deaths by a single infectious agent. Vaccine-development efforts are extremely important. This paper represents the results of the first-in-human trial of recombinant subunit tuberculosis vaccine GamTBvac in a Phase I study.

Biotransformation of progesterone by Aspergillus nidulans VKPM F-1069 (wild type).

Biotechnological transformation of steroids using enzyme systems of microorganisms is often the only possible method to modify the molecule in the industrial production of steroid drugs. Filamentous fungus Aspergillus nidulans has been little studied as a steroid-transforming microorganism. We studied the ability of the A.

Broad Bactericidal Activity of the Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens.

The extremely rapid spread of multiple-antibiotic resistance among Gram-negative pathogens threatens to move humankind into the so-called "post-antibiotic era" in which the most efficient and safe antibiotics will not work. Bacteriophage lysins represent promising alternatives to antibiotics, as they are capable of digesting bacterial cell wall peptidoglycans to promote their osmotic lysis. However, relatively little is known regarding the spectrum of lysin bactericidal activity against Gram-negative bacteria.