Anti-SARS-CoV-2 Activity of a Polyphenolic Complex from Maackia amurensis.

We studied the ability of the polyphenolic complex from Maackia amurensis, the active substance of Maksar, to inhibit the cytopathogenic effect induced by the SARS-CoV-2 and to reduce the concentration of viral RNA in infected Vero E6 cells. Polyphenolic complex showed significant anti-SARS-CoV-2 activity and effectively inhibited viral replication by direct action on viral particles and the early stage of viral infection.

The prevalence and risk factors of canine demodicosis: A retrospective long-term study of 409 cases.

Canine demodicosis is a common skin disorder with multiple risk factors, including age and breed predisposition. There is relatively limited information about the risk factors for canine demodicosis in large canine populations. This retrospective case-control study was conducted by searching the electronic records of dogs with skin lesions for the presence of Demodex mites in skin scrapings. Diagnosis of demodicosis was based on the presence of skin lesions and mites in skin scrapings. Multivariate analysis was conducted using logistic regression analysis to estimate the relative risk and odds ratio of variables hypothesized to influence the risk of canine demodicosis, such as age, sex, breed, season, and parasitic infection. The results of multivariate logistic regression analysis showed a positive correlation between the dogs' age and demodicosis. Dogs older than three years, as well as puppies, had a high risk of demodicosis (P0.05). Breeds with the greatest association (odds ratio) with demodicosis included the American Staffordshire Terrier (OR=0.9) and Moscow Watchdog (OR=0.2). The presence of intestinal parasites, such as Diphyllobothrium latum, was significantly associated with demodicosis.

Amino acid polymorphism at residue 222 of the receptor-binding site of the hemagglutinin of the pandemic influenza A(H1N1)pdm09 from patients 166 with lethal virus pneumonia in 2012-2014.

Survey data from autopsy specimens from patients who died from pneumonia caused by the influenza A(H1N1) pdm09 in 2012-2014 and mutant forms of influenza virus in these patients (position 222 in the receptor-binding region of hemagglutinin) were presented. In total, according to aggregate data, obtained with three different methods (sequencing, next-generation sequencing (NGS), virus isolation) mutant viruses were detected in 17 (41%) from 41 patients. The proportion of the mutant forms in viral populations ranged from 1% to 69.2%. The most frequent mixture was the wild type (D222) and mutant (D222G), with proportion of mutant type ranged from 3.3% to 69.2% in the viral population. Mutation D222N (from 1.1% to 5.5%) was found rarely. Composition of the viral population from one patient is extremely heterogeneous: in left lung there was only wild type D222, meantime in right lung - mixture of mutant forms 222D/N/G (65.4/32.5/1.1%), in trachea - mixture 222D/G/Y/A (61.8/35.6/1.2/1.4%, respectively), and in bronchi compound of 222D/G/N/A (64.3/33.7/1/1%, respectively) were detected. The obtained data indicate that the process of adaptation of the virus in the lower respiratory tract is coupled with the appearance of different virus variants with mutations in the receptor-binding region. Mutant forms of the virus are observed in the lower respiratory tract of the majority of patients with lethal viral pneumonia. However, if they are a minor part of the population, they cannot be detected by the method of conventional sequencing. They can be identified using the NGS methods.

Isolation and complete genome sequencing of rabies virus strain isolated from a brown bear (Ursus arctos) that attacked a human in Primorsky krai (November, 2014).

An attack of a brown bear (Ursus arctos) on human was detected in November, 2014 in the Barabash village (Khasan region of the Primorski krai) located in close proximity to the national park Land of the Leopard. The bear was shot. The deviant behavior of the bear indicated the possibility of rabies. The diagnosis was confirmed by means of laboratory methods. The strain RABV/Ursus arctos/Russia/Primorye/PO 01/2014 (further PO 01) was isolated from the brain of the bear. PO 01 is the first completely sequenced Far Eastern strain of RABV. It can be considered as topotypic. PO 01 considerably differs from the vaccine strain RV 97 (GenBank EF542830) that is the basis of attenuated vaccine applied in the Land of the Leopard. At the same time, the immunodominant sites in PO 01 and RV 97 proteins differ slightly. It can be recommended to continue application of the vaccine. The analysis of the PO 01 genome (GenBank KP997032) revealed its belonging to the Eurasian genetic subgroup of the genotype 1 (street rage). Thus, this genetic subgroup stretches to the East. Expansion of the cross-border protected territories of Russia and China in the Far East demands the correct statistics of circulation of the lyssaviruses to be kept.

Evolution of influ- 245 enza A/H5N1 virus (1996-2016).

Twenty years ago in the South Chinese province of Guangdong the epizooty of highly pathogenic avian influenza (HPAI) H5N1 virus, which has laid the foundation of the largest epizooty in the contemporary history, has flashed. Hemagglutinin of prototype A/goose/Guangdong/1/1996 (H5N1) changing many times and generating new genetic subgroups participated in various reassortations; it still exists today. The present review is devoted to the retrospective analysis of HPAI/H5N1evolution for the last twenty years in the territory of Eurasia, Africa and America. The basis for the discussion is ecological model according to which new genetic variants are formed in the migration pathways with close contacts between different bird populations and in the overwintering areas where the maximum values of the immune layer occur; amplification of virus variants occurs in nesting areas among juvenile populations. The updated system of designations of genetic groups introduced by WHO/OIE/FAO H5 Evolution Working Group in 2015 is used.

West Nile virus and other zoonotic viruses in Russia: examples of emerging-reemerging situations.

Studies of the interactions of vertebrates, viruses and arthropod vectors of these viruses were monitored in terms of different ecological groups of viruses transmitted by mosquitoes and ticks in Northern Eurasia in an area encompassing more than 15 million km2. About 90 viruses were isolated, including 24 new to science. Newly recognized infections of vertebrates, including humans, were described. Many unusual epidemic situations were analysed. Permanent efforts were established to prevent bioterrorist activities and their consequences. Extensive epidemic outbreaks of West Nile fever (WNF; i.e., fever caused by West Nile virus) and Crimean-Congo hemorrhagic fever (CCHF) with unusual high mortality appeared in the last four years in southern Russia. We determined infection rates in humans, domestic and wild animals, mosquitoes and ticks from natural and synanthropic biocenoses [Editorial note: "synanthropic" means, roughly, all species living with (c.f. lice, fleas) or near people, such as in houses (c.f. house mice), parks (c.f. Rattus spp.), and the like, rather like "peridomestic", but not strictly so; "biocenosis" is the biome, the "totality of living populations in a particular habitat, which itself is only a part of the ecosystem".]. CCHF virus strains were phylogenetically similar to strains isolated in this area 35 years ago but different from Central-South-Asian and African strains. Before the outset of the current emergence of epidemic WNF, three genetic variants of this virus had been isolated in USSR, two African and one Indian. Phylogenetic analysis of complete genome sequences of epidemic strains demonstrated considerable similarity to strains from USA and Israel and differences from strains isolated in the same USSR areas 20-30 years before. In addition to strains of genotype 1, we isolated strains of second and third lineages and a strain of a fourth genetic variant. Nucleotide differences of these strains from all three genotypes was about 30%. The emerging WNF situation in Russia for the last 4 years probably has been the result of not only natural and social factors, but also to introduction of more virulent strains or by evolution of the virus.

Basic properties of populations generated in the frame of one-parameter discrete model of genetic diversity.

Previously, when discussing the properties of one parameter discrete model of genetic diversity (M.Yu. Shchelkanov et al, J. Biomol. Struct. Dyn. 15, 887-894 (1998)), we took into account Hamming distance distribution only between precursor and arbitrary descendant sequences. However, really there are sets of sequence populations produced during amplification process. In the presented work we have investigated Hamming distance distributions between sequences from different descendant sets produced in the frame of one parameter discrete model. Two basic descendant generation operators (so called amplifiers) are introduced: 1) the last generation amplifier, L, which produces descendants with precursor elimination; 2) all generations amplifier, G, which produces descendants without precursor elimination. Generalization of one-parameter discrete model for the case when precursor sequences do not coincide are carried out. Using this generalization we investigate the distribution of Hamming distances between L- and G-generated sequences. Basic properties of L and G operators, L/G-choice alternative problem have been discussed. Obtained results have common theoretical significance, but they are more suitable for high level genetic diversity process (for example, HIV diversity).

Dehydrogenase activity of infected cells and biological properties of HIV-1 variants.

Changes in dehydrogenase activity of some continuous cell lines were studied during the response to acute infection in vitro with HIV-1 variants having different biological features. Soon after infection, the dehydrogenase activity of infected cells increased, and this increase was greater and more prolonged with the HIV-1 r/h variant than with the HIV-1 s/l variant. Later stages showed decreased dehydrogenase activity of HIV-1-infected cells compared to the noninfected control; this is a manifestation of the cytodestructive effect of the virus. The changes increased monotonously (but not in direct proportion) with an increase in the infecting dose.

Stochastic properties of one-parameter discrete model of genetic diversity in the unique random parameter case.

Stochastic properties of previously introduced one parameter discrete model of genetic diversity (M. Yu. Shchelkanov et al, J. Biomol. Struct. Dyn. 15, 887-894 (1998)) are investigated. Two approaches are compared: (A) when the on-step substitution number and/or the number of substitution steps are random variables; (B) referred parameters are replaced by mathematical expectations of the respective variables. It has been demonstrated, that estimations of sequence measure based on the number of replication steps are more under the assumption of case (A) as compared with (B). Thus, real biological situation relating to the case (A) could additionally promote the increasing of distinctions between different taxons (e.g. HIV, etc.). Peculiarities of one-parameter discrete model of genetic diversity during calculation of the distinctions between symbol (e.g. nucleotide) sequence sets are also discussed.

Dependencies of substitution steps number on Hamming distance are identical for one-parameter discrete models of both direct and parallel genetic diversity.

With the help of previously introduced enumeration procedure (M.Yu. Shchelkanov, A.N. Yudin, A.V Antonov, N.S. Starikov, A.A. Vedenov, E.V. Karamov, J. Biomol. Struct. Dyn. 15, 217-229 (1997)) and probability distribution function for the enumeration after some substitution steps (M.Yu. Shchelkanov, L.A. Soinov, V.V. Zalunin, D.A. Gumennyi, A.N. Yudin, A.A. Natan, V.B. Kireev, E.V. Karamov, J. Biomol. Struct. Dyn. 15, N 4, (1998)) we have demonstrated that dependencies of replication acts number on Hamming distance are identical for one-parameter discrete models of both direct and parallel genetic diversity.