Inhibitory Effect of Phosphorothioate Oligonucleotide Complementary to G6PD mRNA on Murine Melanoma.

In terms of the incidence among all tumors, skin cancer is on top, with the most deadly among them being melanoma. The search for new therapeutic agents to combat melanoma is very relevant. In our opinion, antisense oligonucleotides (ASO) aimed at suppressing the genes responsible for their viability in cancer cells give hope for treatment, which makes it possible to eliminate cancer cells near the tumor site both before and after surgery. In this article, we describe how Skeen-11 phosphorothioate oligonucleotide significantly decreased the proliferative activity of murine melanoma cells. Injections of Skeen-11 also inhibited tumor growth in mice with inoculated melanoma. A toxicity study showed no side effects with dose adjustments. The results show that the use of ASO Skeen-11 in vivo reduced the tumor size within 7 days, reduced the number of mitoses in the tumor cells, and increased the amount of necrosis compared with the control group.

Biological Properties and Genetic Characterization of Novel Low Pathogenic H7N3 Avian Influenza Viruses Isolated from Mallard Ducks in the Caspian Region, Dagestan, Russia.

Avian influenza viruses (AIVs) are maintained in wild bird reservoirs, particularly in mallard ducks and other waterfowl. Novel evolutionary lineages of AIV that arise through genetic drift or reassortment can spread with wild bird migrations to new regions, infect a wide variety of resident bird species, and spillover to domestic poultry. The vast continental reservoir of AIVs in Eurasia harbors a wide diversity of influenza subtypes, including both highly pathogenic (HP) and low pathogenic (LP) H7 AIV. The Caspian Sea region is positioned at the intersection of major migratory flyways connecting Central Asia, Europe, the Black and Mediterranean Sea regions and Africa and holds a rich wetland and avian ecology. To understand genetic reservoirs present in the Caspian Sea region, we collected 559 cloacal swabs from Anseriformes and other species during the annual autumn migration periods in 2017 and 2018. We isolated two novel H7N3 LPAIV from mallard ducks whose H7 hemagglutinin (HA) gene was phylogenetically related to contemporaneous strains from distant Mongolia, and more closely Georgia and Ukraine, and predated the spread of this H7 LPAIV sublineage into East Asia in 2019. The N3 neuraminidase gene and internal genes were prototypical of AIV widely dispersed in wild bird reservoirs sampled along flyways connected to the Caspian region. The polymerase and nucleoprotein segments clustered with contemporaneous H5 HPAI (clade 2.3.4.4b) isolates, suggesting the wide dispersal of H7 LPAIV and the potential of this subtype for reassortment. These findings highlight the need for deeper surveillance of AIV in wild birds to better understand the extent of infection spread and evolution along spatial and temporal flyways in Eurasia.

Intratumoral Virotherapy with Wild-Type Newcastle Disease Virus in Carcinoma Krebs-2 Cancer Model.

The results of experimental and clinical trials of the agents based on oncolytic Newcastle disease virus (NDV) strains provided hope for the development of virotherapy as a promising method for treating human tumors. However, the mechanism of the antitumor effect of NDV and realization of its cytotoxic potential in a cancer cell remains to be elucidated. In the current work, we have studied the antitumor effect of NDV in a syngeneic model of mouse Krebs-2 carcinoma treated with intratumoral injections of a wild-type strain NDV/Altai/pigeon/770/2011. Virological methods were used for preparation of a virus-containing sample. Colorimetric MTS assay was used to assess the viability of Krebs-2 tumor cells infected with a viral strain in vitro. In vivo virotherapy was performed in eight-week-old male BALB/c mice treated with serial intratumoral injections of NDV in an experimental model of Krebs-2 solid carcinoma. Changes in the tumor nodes of Krebs-2 carcinoma after virotherapy were visualized by MRI and immunohistological staining. Light microscopy examination, immunohistochemical and morphometric analyses have shown that intratumoral viral injections contribute to the inhibition of tumor growth, appearance of necrosis-like changes in the tumor tissue and the antiangiogenic effect of the virus. It has been established that a course of intratumoral virotherapy with NDV/Altai/pigeon/770/2011 strain in a mouse Krebs-2 carcinoma resulted in increased destructive changes in the tumor tissue, in the volume density of necrotic foci and numerical density of endothelial cells expressing CD34 and VEGFR. These results indicate that intratumoral NDV injection reduces tumor progression of an aggressive tumor.

Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression.

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund's adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

SARS-CoV-2 will continue to circulate in the human population: no worries with state-of-the-art research and dependably useful results.

This short article provides additional justification for our understanding of the virus-host relationship in the population. Some new data are presented concerning viral structure/behavior and a critical assessment on the possibilities of using new approaches for the treatment of patients with COVID-19.

SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship.

At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain in the host population. In turn, the virus can never completely eliminate the host population, because evolutionarily such an event is a dead end for the virus as an obligate intracellular parasite. A certain existential balance exists in the virus-host relationship. Against this backdrop, viral epidemics and pandemics only become manifest and egregious to human beings when tens and hundreds of thousands of people die and the question emerges what caused the high mortality peaks on the death chart. The answer seems clear; the emerging strain of the virus is new to the host population, and new mutations of the virus and natural selection will lead to a survival of only genetically resistant individuals in a host population. The dangers inherent to a novel virus are due to new features generally inthe molecular structure of proteins, which enable the virus to infect the cells of the host organism more intensively, dramatically challenging host immunity, and thus be transmitted more readily in the host population. In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In fact, only two scenarios will occur simultaneously in the very near future: people who are genetically resistant to the virus will get sick, recover, and develop immunity, while people who are sensitive to the virus will need drugs and vaccines, which will have to be researched and developed if they are to recover. If the pandemic does not stop, in a few decades it is anticipated that SARS-CoV-2 will become as safe as the four non-severe acute respiratory syndrome human coronaviruses (HCoV-NL63, HCoV-HKU1, HCoV-OC43, and HCoV-229E) currently circulating but causing low mortality in the human population.

Nearly Complete Genome Sequence of a Newcastle Disease Virus Strain Isolated from a Wild Garganey (Spatula querquedula) in Russia.

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.

Oncolytic effect of wild-type Newcastle disease virus isolates in cancer cell lines in vitro and in vivo on xenograft model.

Oncolyic virotherapy is one of the modern experimental techniques to treat human cancers. Here we studied the antitumor activity of wild-type Newcastle disease virus (NDV) isolates from Russian migratory birds. We showed that NDV could selectively kill malignant cells without affecting healthy cells. We evaluated the oncolytic effect of 44 NDV isolates in 4 histogenetically different human cell lines (HCT116, HeLa, A549, MCF7). The safety of the isolates was also tested in normal peripheral blood mononuclear (PBMC) cells. The viability of tumor cell lines after incubation with NDV isolates was evaluated by MTT. All cell lines, except for normal PBMC primary cells, had different degrees of susceptibility to NDV infection. Seven NDV strains had the highest oncolytic activity, and some NDV strains demonstrated oncolytic selectivity for different cell lines. In vivo, we described the intratumoral activity of NDV/Altai/pigeon/770/2011 against subcutaneous non-small cell lung carcinoma using xenograft SCID mice model. All animals were responsive to therapy. Histology confirmed therapy-induced destructive changes and growing necrotic bulk density in tumor tissue. Our findings indicate that wild-type NDV strains selectively kill tumor cells with no effect on healthy PBMC cells, and intratumoral virotherapy with NDV suppresses the subcutaneous tumor growth in SCID mice.

Complete Genome Sequences of Two Newcastle Disease Virus Strains Isolated from a Wild Duck and a Pigeon in Russia.

Here, we report the complete genome sequences of two Newcastle disease virus (NDV) isolates, Adygea/duck/12/2008, from a wild duck in Russia, and Altai/pigeon/777/2010, from a pigeon in Russia. Based on comparative sequence analysis of the F gene, these strains were classified as NDV class II, genotypes VIId and VIb/2, respectively.

Characterization of avian paramyxovirus type 6 isolated from a Eurasian teal in the intersection of migratory flyways in Russia.

The complete genome sequence was determined for avian paramyxovirus (APMV-6) serotype 6 strain teal/Chany/455/2009, isolated from a teal (Anas crecca) in Siberia. Siberia is crossed by four major migration flyways and represents the major breeding area for many wild bird species in the Palearctic. Strain teal/Chany/455/2009 is genetically closely related to Kazakh and Chinese strains and belongs to the genetic group of duck/Hong Kong/18/199/77-like APMV-6 viruses. We show that the virus has low pathogenic potential according to genetic markers and animal model experiments.

Complete Genome Sequence of Genotype Ib Newcastle Disease Virus Isolated from a Mallard (Anas platyrhynchos) in Russia.

We report here the complete genome sequence of a Newcastle disease virus isolate, NDV/Yakutiya/mallard/852/2011, isolated from a mallard in Russia. On the basis of phylogenetic analysis, this strain was clustered into class II genotype Ib.

Complete Genome Sequence of a Newcastle Disease Virus Isolated from a Rock Dove (Columba livia) in the Russian Federation.

We report here the complete genome sequence of a Newcastle disease virus (NDV) isolate, NDV/Altai/pigeon/770/2011, isolated from a rock dove in the Russian Federation. On the basis of phylogenetic analysis, this strain was clustered into genotype VIb class II.