To rationalize the antiviral actions of plant alkaloids, the ability of 20 compounds to inhibit calcium-mediated fusion of lipid vesicles composed of phosphatidylglycerol and cholesterol was investigated using the calcein release assay and dynamic light scattering. Piperine, tabersonine, hordenine, lupinine, quinine, and 3-isobutyl-1-methylxanthine demonstrated the most potent effects (inhibition index greater than 50%). The introduction of phosphatidylcholine into the phosphatidylglycerol/cholesterol mixture led to significant changes in quinine, hordenine, and 3-isobutyl-1-methylxanthine efficiency. Comparison of the fusion inhibitory ability of the tested alkaloids, and the results of the measurements of alkaloid-induced alterations in the physical properties of model membranes indicated a potent relationship between a decrease in the cooperativity of the phase transition of lipids and the ability of alkaloids to prevent calcium-mediated vesicle fusion. In order to use this knowledge to combat the novel coronavirus pandemic, the ability of the most effective compounds to suppress membrane fusion induced by fragments of MERS-CoV and SARS-CoV/SARS-CoV-2 fusion peptides was studied using the calcein release assay and confocal fluorescence microscopy. Piperine was shown to inhibit vesicle fusion mediated by both coronavirus peptides. Moreover, piperine was shown to significantly reduce the titer of SARS-CoV2 progeny in vitro in Vero cells when used in non-toxic concentrations.

This paper discusses the possibility of using plant polyphenols as viral fusion inhibitors with a lipid-mediated mechanism of action. The studied agents are promising candidates for the role of antiviral compounds due to their high lipophilicity, low toxicity, bioavailability, and relative cheapness. Fluorimetry of calcein release at the calcium-mediated fusion of liposomes, composed of a ternary mixture of dioleoyl phosphatidylcholine, dioleoyl phosphatidylglycerol, and cholesterol, in the presence of 4′-hydroxychalcone, cardamonin, isoliquiritigenin, phloretin, resveratrol, piceatannol, daidzein, biochanin A, genistein, genistin, liquiritigenin, naringenin, catechin, taxifolin, and honokiol, was performed. It was found that piceatannol significantly inhibited the calcium-induced fusion of negatively charged vesicles, while taxifolin and catechin showed medium and low antifusogenic activity, respectively. As a rule, polyphenols containing at least two OH-groups in both phenolic rings were able to inhibit the calcium-mediated fusion of liposomes. In addition, there was a correlation between the ability of the tested compounds to inhibit vesicle fusions and to perturb lipid packing. We suggest that the antifusogenic action of polyphenols was determined by the depth of immersion and the orientation of the molecules in the membrane.

This work describes the nearly complete genome sequence of Newcastle disease virus (NDV) strain NDV/Novosibirsk/garganey/27/2014, which was isolated from a wild garganey in western Siberia, Russia. The NDV strain was classified as belonging to class II of genotype I and was identified as having recent common ancestry with isolates from wild and domestic birds in China and South Korea.

The life cycle of Ebola and Marburg viruses includes a step of the virion envelope fusion with the cell membrane. Here, we analyzed whether the fusion of liposome membranes under the action of fragments of fusion peptides of Ebola and Marburg viruses depends on the composition of lipid vesicles. A fluorescence assay and electron microscopy were used to quantify the fusogenic activity of the virus fusion peptides and to identify the lipid determinants affecting membrane merging. Differential scanning calorimetry of lipid phase transitions revealed alterations in the physical properties of the lipid matrix produced by virus fusion peptides. Additionally, we found that plant polyphenols, quercetin, and myricetin inhibited vesicle fusion induced by the Marburg virus fusion peptide.

Oncolytic Newcastle disease viruses (NDVs) make up a group of antitumor agents for the experimental treatment of oncological diseases that nonpathogenic for human beings. It is known that realization of the cytotoxic effect of NDV strains on the tumor cells depends on the peculiarities of viral genome structure, strain virulence, and tumor cell culture (National Institutes of Health, 2018). At the same time, the mechanism of NDV-induced death has been poorly studied. The aim of this work was to study the nature of morphological changes in HeLa and Hep-2 (HeLa derivative) human tumor cells after infection with the wild-type mesogenic NDV strain NDV/Altai/pigeon/770/2011. The calculation of living tumor cells using MTT test demonstrated that the cytotoxic activity of NDV/Altai/pigeon/770/2011 strain in 144 h after infection decreases the cell viability till 13.08 ± 8.29% (HeLa) and 4.74 ± 3.29% (Hep-2, HeLa derivative). A routine staining detected morphological traits of degradation of infected cells, while morphometric studies detected an increase in the value of the nuclear–cytoplasmic ratio (NCR). The presence of a virus in the tumor cells was visualized by the method of immunocytochemical staining (ICS) using antibodies to the HN glycoprotein of the NDV envelope. The results of immunodetection of tumor necrosis factor α (TNFα) suggest the activation of cell death along the apoptosis pathway against the background of viral infection. The results obtained indicate a pronounced cytotoxic activity of wild-type NDV/Altai/pigeon/770/2011 strain regarding HeLa and Hep-2 (HeLa derivative) adenocarcinoma cells and sensitivity of the studied cell lines to the oncolytic effect of NDV.