Vol 68, No 1 (2023)


Structural Motifs and Spatial Structures of Helicase (NS3) and RNA-dependent RNA-polymerase (NS5) of a Flavi-like Kindia tick virus (unclassified Flaviviridae)

Gladysheva A.A., Gladysheva A.V., Ternovoi V.A., Loktev V.B.


Introduction. Kindia tick virus (KITV) is a novel segmented unclassified flavi-like virus of the Flaviviridae family. This virus is associated with ixodes ticks and is potentially pathogenic to humans.

The main goal of this work was to search for structural motifs of viral polypeptides and to develop a 3D-structure for viral proteins of the flavi-like KITV.

Materials and methods. The complete genome sequences for KITV, Zika, dengue, Japanese encephalitis, West Nile and yellow fever viruses were retrieved from GenBank. Bioinformatics analysis was performed using the different software packages.

Results. Analysis of the KITV structural proteins showed that they have no analogues among currently known viral proteins. Spatial models of NS3 and NS5 KITV proteins have been obtained. These models had a high level of topological similarity to the tick-borne encephalitis and dengue viral proteins. The methyltransferase and RNA-dependent RNA-polymerase domains were found in the NS5 KITV. The latter was represented by fingers, palm and thumb subdomains, and motifs A-F. The helicase domain and its main structural motifs I–VI were identified in NS3 KITV. However, the protease domain typical of NS3 flaviviruses was not detected. The highly conserved amino acid motives were detected in the NS3 and NS5 KITV. Also, eight amino acid substitutions characteristic of KITV/2018/1 and KITV/2018/2 were detected, five of them being localized in alpha-helix and three in loops of nonstructural proteins.

Conclusion. Nonstructural proteins of KITV have structural and functional similarities with unsegmented flaviviruses. This confirms their possible evolutionary and taxonomic relationships.

Problems of Virology. 2023;68(1):7-17
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Antiviral properties of synthetic histidine derivatives containing membranotropic volumetrical carbocycles in their molecule against SARS-CoV-2 virus in vitro

Garaev T.M., Grebennikova T.V., Avdeeva V.V., Lebedeva V.V., Larichev V.F.


Introduction. Currently, low molecular-weight compounds are being developed as potential inhibitors of CoVs replication, targeting various stages of the replication cycle, such as major protease inhibitors and nucleoside analogs. Viroporins can be alternative protein targets.

The aim of this study is to identify antiviral properties of histidine derivatives with cage substituents in relation to pandemic strain SARS-CoV-2 in vitro.

Materials and methods. Combination of histidine with aminoadamantane and boron cluster anion [B10H10]2– (compounds I–IV) was carried out by classical peptide synthesis. Compound were identified by modern physicochemical methods. Antiviral properties were studied in vitro on a monolayer of Vero E6 cells infected with SARS-CoV-2 (alpha strain) with simultaneous administration of compounds and virus.

Results. Derivatives of amino acid histidine with carbocycles and boron cluster were synthesized and their antiviral activity against SARS-CoV-2 was studied in vitro. Histidine derivatives with carbocycles and [B10H10]2– have the ability to suppress virus replication. The solubility of substances in aqueous media can be increased due to formation of hydrochloride or sodium salt.

Discussion. 2HCl*H-His-Rim (I) showed some effect of suppressing replication of SARS-CoV-2 at a viral load of 100 doses and concentration 31.2 μg/ml. This is explained by the weakly basic properties of compound I.

Conclusion. The presented synthetic compounds showed moderate antiviral activity against SARS-CoV-2. The obtained compounds can be used as model structures for creating new direct-acting drugs against modern strains of coronaviruses.

Problems of Virology. 2023;68(1):18-25
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In vitro activity of human recombinant interferon gamma against SARS-CoV-2 virus

Nikolaeva Y.V., Galochkina A.V., Shtro A.A., Berns S.A.


Introduction. The development of drugs against SARS-CoV-2 continues to be crucial for reducing the spread of infection and associated mortality.

The aim of the work is to study the neutralization of the SARS-CoV-2 virus with interferon gamma preparations in vitro.

Materials and methods. The activity of recombinant human interferon gamma for intramuscular and subcutaneous administration of 500,000 IU and for intranasal administration of 100,000 IU against the SARS-CoV-2 virus in vitro was studied. The methodological approach of this study is based on the phenomenon of a decrease in the number of plaques formed under the action of a potential antiviral drug.

Results. The antiviral activity of recombinant interferon gamma has been experimentally confirmed, both in preventive and therapeutic application schemes. The smallest number of plaques was observed with the preventive scheme of application of the tested object at concentrations of 1000 and 333 IU/ml. The semi-maximal effective concentration (EC50) with the prophylactic regimen was 24 IU/ml.

Discussion. The preventive scheme of application of the tested object turned out to be more effective than therapeutic one, which is probably explained by the launch of the expression of various interferon-stimulated genes that affect to a greater extent the steps of virus entry into the cell and its reproduction.

Conclusion. Further study of the effect of drugs based on recombinant interferon gamma on the reproduction of the SARS-CoV-2 virus for clinical use for prevention and treatment is highly relevant.

Problems of Virology. 2023;68(1):26-36
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The incidence of infection in tumor and eye fluid system, and specific humoral immunity to herpes viruses in patients with uveal melanoma

Svetlova E.V., Balatskaya N.V., Saakyan S.V., Zharov A.A., Krichevskaya G.I., Svirina I.V., Izmailova N.S., Myakoshina E.B.


Introduction. Studies aimed at a direct research of human herpes viruses (HHVs) in the tumor material and eye media have not been carried out so far.

Research goal – to establish the frequency of detection HHVs DNA in the biomaterial of the eye and blood and to assess the specific humoral immunity to the causative agents of herpes virus infections in patients with uveal melanoma.

Materials and methods. 38 patients with the uveal tract tumor were examined for the presence of DNA of HHV types 1 and 2 (HSV-1, 2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV), Epstein–Barr virus (EBV) and herpes viruses 6 and 8 types (HHV-6, HHV-8) in tumor tissue, vitreous body, aqueous humour and blood plasma by real-time polymerase chain reaction; blood serum was studied by enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies to HHVs.

Results. EBV DNA was present in tumor tissue in 20.6% of cases, in vitreous body in 4.2%, in blood plasma in 2.7%, and was not found in aqueous humor. Ig G antibodies to HSV-1, 2 and CMV were detected in 97.3% of cases, VZV – 94.6%, HHV-6 – 32.4%, antibodies to HHV-8 were not detected. 20 patients (55.6%) had reactivation of chronic HSV-1, 2 infection, and 14 (38.9%) patients had reactivation of CMV infection. Markers of chronic EBV infection were found in all patients, its atypical reactivation was observed in 2 cases (5.4%).

Conclusion. Our findings suggest the possible participation of EBV in the oncogenesis of the uveal tract and emphasize the need for further in-depth study of this problem.

Problems of Virology. 2023;68(1):37-44
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Lethal cases of lyssavirus encephalitis in humans after contact with bats in the Russian Far East in 2019–2021

Poleshchuk E.M., Tagakova D.N., Sidorov G.N., Orlova T.S., Gordeiko N.S., Kaisarov A.Z.


Introduction. On the territory of Russia four species of lyssaviruses (genus Lyssavirus) were identified, three of them caused human deaths.

The aim of work: to characterize fatal cases in humans after contacts with bats in the Far East in 2018–2021 and to perform typing of isolated pathogens.

Materials and methods. Lyssavirus infection was confirmed in samples of sectional material from people who died in the Amur Region in 2019, in the Primorsky Krai in 2019 and 2021. Diagnostics was performed by fluorescent antibody test (FAT) and RT-PCR using diagnostic kits of domestic production. Viruses were isolated in a bioassay. The nucleoprotein sequences were analyzed after 1st passage. The analysis of phylogenetic relationships and the construction of a dendrogram were performed using the MEGA7 software.

Results. The viruses that caused the fatal cases in humans in the Amur Region and Primorsky Krai share more than 90% identity to Lyssavirus irkut detected in Russia and China. Together they form a separate monophyletic cluster with 100% bootstrap support.

Conclusion. On the territory of Russia, monitoring of bat populations for infection with lyssaviruses is relevant. The material of people who died from encephalomyelitis of unknown etiology within 10–15 days from the onset of the disease must be examined for lyssavirus infection. It is necessary to develop PCR assays that employ genus-specific primers. The use of molecular biological methods is promising for improving the diagnosis of rabies and epidemiological surveillance, as well as increasing the efficiency of the system of biological safety of the population of the Russian Federation.

Problems of Virology. 2023;68(1):45-58
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Mumps virus (Paramyxoviridae: Orthorubulavirus: Mumps orthorubulavirus) genotyping as a component of laboratory confirmation of infection

Rubalskaia T.S., Erokhov D.V., Zherdeva P.E., Milikhina A.V., Gadzhiewa A.A., Tikhonova N.T.


Introduction. Mumps is a viral infection of high social significance. National program «Elimination of measles and rubella and achievement of a stable sporadic incidence of epidemic mumps in the Russian Federation (2021–2025)» sets the aim of gradual integration of mumps surveillance into the existing measles and rubella surveillance system. One of the key components of surveillance system is a laboratory confirmation of mumps cases. There are two approaches for laboratory confirmation of mumps cases, based on serological or molecular genetic methods. The aim of the work is molecular genetic characteristic of the mumps viruses (MuVs) circulated in the Russian Federation in 2022.

Materials and methods. Samples of swabs from the inner surface of the cheek of 11 patients with mumps were collected for the study. Viral RNA was isolated directly from the samples. The isolated RNA was used as a matrix for RT-PCR. PCR products were sequenced using the Sanger method, and phylogenetic analysis was performed using the MEGA-X software.

Results. The MuV genotype G was detected in all samples. Phylogenetic analysis showed the presence of two virus genetic groups G-1 and G-2 that were significantly different from the viruses circulating in other countries.

Conclusion. The identification of two MuV genetic groups in a limited area suggests a high genetic diversity of the pathogen.

Problems of Virology. 2023;68(1):59-65
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Genetic diversity of capsid protein (p24) in human immunodeficiency virus type-1 (HIV-1) variants circulating in the Russian Federation

Kuznetsova A.I., Munchak I.M., Lebedev A.V., Tumanov A.S., Kim K.V., Antonova A.A., Ozhmegova E.N., Pronin A.Y., Drobyshevskaya E.V., Kazennova E.V., Bobkova M.R.


Introduction. The human immunodeficiency virus (HIV) protein p24 plays an important role in the life cycle of the virus, and also is a target for diagnostic tests and for new antiretroviral drugs and therapeutic vaccines. The most studied variant of HIV-1 in the world is subtype B. In Russia, the most common variant is A6, the spread of recombinant forms (CRF63_02A6, CRF03_A6B) is observed as well as circulation of G and CRF02_AG variants. However, a detailed study of the p24 protein in these variants has not yet been conducted.

The aim was to study the features of the p24 protein in HIV-1 variants circulating in Russia and estimate the frequency of occurrence of pre-existing mutations associated with resistance to lenacapavir, the first antiretroviral drug in the class of capsid inhibitors.

Materials and methods. The objects of the study were the nucleotide sequences obtained from the Los Alamos international database and clinical samples from HIV infected patients.

Results and discussion. The features of HIV-1 variants circulating in Russia have been determined. V86A, H87Q, I91F are characteristic substitutions in A6 genome. It is shown that the presence of preexisting mutations associated with resistance to lenacapavir is unlikely.

Conclusion. Features of the p24 protein in HIV-1 variants circulating in Russia allow them to be distinguished from others variants and among themselves. The prognosis for the use of lenacapavir in Russia is generally favorable. The results obtained could be taken into account in developing and using antiretroviral drugs and therapeutic vaccines.

Problems of Virology. 2023;68(1):66-78
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Shrew-borne hantaviruses (Hantaviridae: Orthohantavirus) in the Far East of Russia

Yashina L.N., Ivanov L.I., Kompanets G.G., Zdanovskaya N.I., Kartashov M.Y.


Introduction. Insectivores are newly recognized hantaviral reservoir worldwide. Four distinct shrew-borne hantaviruses (family Hantaviridae) have been identified in two regions located in southern and northern part of the Russian Far East, two genetic variants of Seewis virus (SWSV), Lena River virus (LENV), Kenkeme virus (KKMV) and Yakeshi virus (YKSV). Here, we describe geographic distribution of shrew-borne hantaviruses in southern part of the Russian Far East: Jewish Autonomous region, Khabarovsk Krai, Primorsky Krai and Sakhalin region.

Materials and methods. Lung samples from shrews of genus Sorex, captured in the four regions of Far Eastern Russia, were examined for hantavirus RNA using reverse transcription polymerase chain reaction (RT-PCR). Phylogenetic analysis of the partial nucleotide sequences of viral genome was conducted using MEGA X software.

Results. New genetic variant of YKSV was identified in new reservoir host, long-clawed shrew (S. ungiuculatus) from Sakhalin Island. Genetic variant of SWSV, ARTV-Sc, has been found to circulate among S. caecutiens on the seacoast of Khabarovsk and Primorsky Krai. KKMV virus and second genetic variant of SWSV, ARTV-St, were found in S. roboratus and S. tundrensis, respectively from Jewish Autonomous region.

Conclusion. Sorex-borne hantaviruses were found in all studied regions of Far Eastern Russia. Our results demonstrated co-evolution of SWSV, KKMV, and YKSV viruses throughout the geographic distribution of its hosts.

Problems of Virology. 2023;68(1):79-85
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To the 80th anniversary of Vladimir I. Zlobin

Problems of Virology. 2023;68(1):86-87
pages 86-87 views


Sviatoslav G. Cheshik

Problems of Virology. 2023;68(1):88-88
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