Photochemical Synthesis of Silver Hydrosol Stabilized by Carbonate Ions and Study of Its Bactericidal Impact on Escherichia coli: Direct and Indirect Effects

The great attention paid to silver nanoparticles is largely related to their antibacterial and antiviral effects and their possible use as efficient biocidal agents. Silver nanoparticles are being widely introduced into various areas of life, including industry, medicine, and agriculture. This leads to their spreading and entering the environment, which generates the potential risk of toxic effect on humans and other biological organisms. Proposed paper describes the preparation of silver hydrosols containing spherical metal nanoparticles by photochemical reduction of Ag+ ions with oxalate ions. In deaerated solutions, this gives ~10 nm particles, while in aerated solutions, ~20 nm particles with inclusion of the oxide Ag2O are obtained. Nanoparticles inhibit the bacterium Escherichia coli and suppress the cell growth at concentrations of ~1 × 10−6–1 × 10−4 mol L−1. Silver particles cause the loss of pili and deformation and destruction of cell membranes. A mechanism of antibacterial action was proposed, taking into account indirect suppressing action of Ag+ ions released upon the oxidative metal dissolution and direct (contact) action of nanoparticles on bacterial cells, resulting in a change in the shape and destruction of the bacteria.

PPAR Ligands Induce Antiviral Effects Targeting Perturbed Lipid Metabolism during SARS-CoV-2, HCV, and HCMV Infection

The manipulation of host metabolisms by viral infections has been demonstrated by several studies, with a marked influence on the synthesis and utilization of glucose, nucleotides, fatty acids, and amino acids. The ability of virus to perturb the metabolic status of the infected organism is directly linked to the outcome of the viral infection. A great deal of research in recent years has been focusing on these metabolic aspects, pointing at modifications induced by virus, and suggesting novel strategies to counteract the perturbed host metabolism. In this review, our attention is turned on PPARs, nuclear receptors controlling multiple metabolic actions, and on the effects played by PPAR ligands during viral infections. The role of PPAR agonists and antagonists during SARS-CoV-2, HCV, and HCMV infections will be analyzed.

Potential of germanium-based compounds in coronavirus infection

The first germanium compounds which exhibited immunomodulatory and antiviral effects were sesquioxane-type germanates. To date, more than a dozen compounds containing germanium have been synthesized and are being actively studied. They include germanium carboxylates and citrates, complexes of germanium with resveratrol, daphnetin, mangiferin, chrysin, quercetin, ascorbic and nicotinic acids, amino acids, gamma-lactones, germanium-containing spirulina, yeast and others. Germanium-based compounds have shown the ability to influence the replication of various DNA/RNA viruses, stimulate the body’s natural resistance, prevent the development of metabolic intoxication of various origin, increase the efficacy of vaccines, and prevent the development of excessive accumulation of reactive oxygen species, which plays a decisive role in the development of inflammatory response caused by a viral infection. It seems reasonable to say that germanium-based complex compounds effectively contribute to the preservation of high--energy bonds in the form of ATP, optimize the activity of metabolic processes by re-oxygenation, and exhibit antimicrobial activity. The purpose of this review is to summarize the pharmacological potential of various germanium-based compounds studied nowadays, taking into account their mechanisms of action, and to analyze their prospects in the development of integrated approaches in the prevention and treatment of SARS-CoV-2 infection.

Evasion of I Interferon-Mediated Innate Immunity by Pseudorabies Virus

Type I interferon (IFN-I) mediated innate immunity serves as the first line of host defense against viral infection, ranging from IFN-I production upon viral detection, IFN-I triggered signaling pathway that induces antiviral gene transcription the antiviral effects of IFN-I induced gene products. During coevolution, herpesviruses have developed multiple countermeasures to inhibit the various steps involved to evade the IFN response. This mini-review focuses on the strategies used by the alphaherpesvirus Pseudorabies virus (PRV) to antagonize IFN-I mediated innate immunity, with a particular emphasis on the mechanisms inhibiting IFN-I induced gene transcription through the JAK-STAT pathway. The knowledge obtained from PRV enriches the current understanding of the alphaherpesviral immune evasion mechanisms and provides insight into the vaccine development for PRV control.

The Petasites hybridus CO2-extract (Ze 339) blocks SARS-CoV-2 replication in vitro

The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2-extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE- and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2 infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, repectively. The IC50 values obtained for isopetasin ranged between 0.37-0.88 μM for both virus variants, that of remdesivir between 1.53-2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-Cov-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections.

Exosomes/microvesicles target SARS-CoV-2 via innate and RNA-induced immunity with PIWI-piRNA system

Murine neural stem cells (NSCs) were recently shown to release piRNA-containing exosomes/microvesicles (Ex/Mv) for exerting antiviral immunity, but it remains unknown if these Ex/Mv could target SARS-CoV-2 and whether the PIWI-piRNA system is important for these antiviral actions. Here, using in vitro infection models, we show that hypothalamic NSCs (htNSCs) Ex/Mv provided an innate immunity protection against SARS-CoV-2. Importantly, enhanced antiviral actions were achieved by using induced Ex/Mv that were derived from induced htNSCs through twice being exposed to several RNA fragments of SARS-CoV-2 genome, a process that was designed not to involve protein translation of these RNA fragments. The increased antiviral effects of these induced Ex/Mv were associated with increased expression of piRNA species some of which could predictably target SARS-CoV-2 genome. Knockout of piRNA-interacting protein PIWIL2 in htNSCs led to reductions in both innate and induced antiviral effects of Ex/Mv in targeting SARS-CoV-2. Taken together, this study demonstrates a case suggesting Ex/Mv from certain cell types have innate and adaptive immunity against SARS-CoV-2, and the PIWI-piRNA system is important for these antiviral actions.