Virucidal Coatings Active Against SARS-CoV-2.

Three types of coatings (contact-based, release-based, and combined coatings with both contact-based and release-based actions) were prepared and tested for the ability to inactivate SARS-CoV-2. In these coatings, quaternary ammonium surfactants were used as active agents since quaternary ammonium compounds are some of the most commonly used disinfectants. To provide contact-based action, the glass and silicon surfaces with covalently attached quaternary ammonium cationic surfactant were prepared using a dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride modifier.

Polyamine Catabolism Revisited: Acetylpolyamine Oxidase Plays a Minor Role due to Low Expression.

Biogenic polyamines are ubiquitous compounds. Dysregulation of their metabolism is associated with the development of various pathologies, including cancer, hyperproliferative diseases, and infections. The canonical pathway of polyamine catabolism includes acetylation of spermine and spermidine and subsequent acetylpolyamine oxidase (PAOX)-mediated oxidation of acetylpolyamines (back-conversion) or their direct efflux from the cell.

Nucleoside Analogs That Inhibit SARS-CoV-2 Replication by Blocking Interaction of Virus Polymerase with RNA.

The SARS-CoV-2 betacoronavirus pandemic has claimed more than 6.5 million lives and, despite the development and use of COVID-19 vaccines, remains a major global public health problem. The development of specific drugs for the treatment of this disease remains a very urgent task.

SARS-CoV-2 Establishes a Productive Infection in Hepatoma and Glioblastoma Multiforme Cell Lines.

Severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and rapidly caused a pandemic that led to the death of >6 million people due to hypercoagulation and cytokine storm. In addition, SARS-CoV-2 triggers a wide array of pathologies, including liver dysfunction and neurological disorders. It remains unclear if these events are due to direct infection of the respective tissues or result from systemic inflammation.

The Effects of HS and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo.

The ongoing epidemic caused by SARS-CoV-2 infection led to the search for fundamentally new ways and means to combat inflammation and other pathologies caused by this virus. Using a cellular model of lipopolysaccharide (LPS)-induced sepsis (human promonocytes), we showed that both a hydrogen sulfide donor (sodium thiosulfate, STS) and a recombinant Heat shock protein 70 (rHsp70) effectively block all major inflammatory mediators when administrated before and after LPS challenge. The protective anti-inflammatory effect of rHsp70 and HS was also confirmed in vivo using various animal models of pneumonia.

Antiseptic Polymer-Surfactant Complexes with Long-Lasting Activity against SARS-CoV-2.

Antiseptic polymer gel-surfactant complexes were prepared by incorporating the low-molecular-weight cationic disinfectant cetylpyridinium chloride into the oppositely charged, slightly cross-linked polymer matrices. Three types of polymers were used: copolymers of acrylamide and sodium 2-acrylamido-2-methylpropane sulfonate; copolymers of acrylamide and sodium methacrylate; copolymers of vinylpyrrolidone and sodium methacrylate. It was shown that the rate of the release of the cationic disinfectant from the oppositely charged polymer gels could be tuned in a fairly broad range by varying the concentration of the disinfectant, the degree of swelling, and degree of cross-linking of the gel and the content/type of anionic repeat units in the polymer matrix.

Cationic Surfactants as Disinfectants against SARS-CoV-2.

The virucidal activity of a series of cationic surfactants differing in the length and number of hydrophobic tails (at the same hydrophilic head) and the structure of the hydrophilic head (at the same length of the hydrophobic n-alkyl tail) was compared. It was shown that an increase in the length and number of hydrophobic tails, as well as the presence of a benzene ring in the surfactant molecule, enhance the virucidal activity of the surfactant against SARS-CoV-2. This may be due to the more pronounced ability of such surfactants to penetrate and destroy the phospholipid membrane of the virus.

Cultivation of Cells in a Physiological Plasmax Medium Increases Mitochondrial Respiratory Capacity and Reduces Replication Levels of RNA Viruses.

Changes in metabolic pathways are often associated with the development of various pathologies including cancer, inflammatory diseases, obesity and metabolic syndrome. Identification of the particular metabolic events that are dysregulated may yield strategies for pharmacologic intervention. However, such studies are hampered by the use of classic cell media that do not reflect the metabolite composition that exists in blood plasma and which cause non-physiological adaptations in cultured cells.

Adjuvantation of an Influenza Hemagglutinin Antigen with TLR4 and NOD2 Agonists Encapsulated in Poly(D,L-Lactide-Co-Glycolide) Nanoparticles Enhances Immunogenicity and Protection against Lethal Influenza Virus Infection in Mice.

Along with their excellent safety profiles, subunit vaccines are typically characterized by much weaker immunogenicity and protection efficacy compared to whole-pathogen vaccines. Here, we present an approach aimed at bridging this disadvantage that is based on synergistic collaboration between pattern-recognition receptors (PRRs) belonging to different families. We prepared a model subunit vaccine formulation using an influenza hemagglutinin antigen incorporated into poly-(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with monophosphoryl lipid A (TLR4 agonist) and muramyl dipeptide (NOD2 agonist).

Novel oral anti-influenza prodrug candidate AV5075S.

Objectives: Development of a novel drug candidate with improved activity against influenza virus neuraminidase (NA) compared with currently available therapeutics.

Methods: Synthesized compounds were evaluated in vitro and in vivo. Three-dimensional molecular docking was successfully applied to classify compounds within the series by inhibitory potency.