Introduction. The main characteristic of pathogenicity of SARS-CoV-2 virus is its ability to cause death in sensitive laboratory animals. The absence of lethal animal infection models requires the search for other approaches to assess pathogenicity. Studying infectious processes in guinea pig lungs allows us to identify the features and patterns of the disease, determine significant histological characteristics, and identify the main pathogenic criteria. We aimed to conduct a comparative pathomorphological study of lung tissue in guinea pigs infected with various SARS-CoV-2 variants using morphometric standardized criteria. Materials and methods. We looked at structural changes in the lungs of 96 outbred guinea pigs depending on COVID-19 pathogenesis. The animals were randomly divided into seven experimental and one control groups of 6 males and 6 females each. The experimental groups were intranasally infected with the following SARS-CoV-2 strains: Wuhan, Alpha, Beta, Gamma, Delta, and Omicron (the last one represented by two genetic lineages BA.5.2 and EG.5). The control group was intranasally injected with 0.9% NaCl. The viral load over time was determined with RT-PCR on nasal flushes and infection titer (on Vero E6 cell culture). The animals that survived were removed from the experiment on day 15. Pathomorphological examination was performed with optical microscopy of histological lung specimens. Results. We detected diffuse alveolar damage as a similar pathological feature in the lungs of both patients with COVID-19 and guinea pigs. Significant differences were revealed in the number of pathomorphological signs caused by various genetic variants of COVID-19. The most considerable pathological effect of SARS-CoV-2 on lung tissue was caused by the Gamma variant. We suppose guinea pig lung dystelectasis to be the main marker of pathogenicity of SARS-CoV-2 strains, since this sign differs significantly in SARS-CoV-2 variants and is associated with excessive cytokine activity. Alveolar hemorrhagic syndrome is characteristic of all the studied coronavirus variants except for Omicron EG.5. The genetic lineages of the omicron variant have a minimal pathological effect on lung tissue and do not cause death in guinea pigs. Conclusion. Guinea pig is an appropriate animal for a SARS-CoV-2 model. Pathomorphological changes in the lungs depend on the SARS-CoV-2 variant causing them. Keywords: SARS-CoV-2, COVID-19, guinea pig, lungs, pathomorphology, SARS-CoV-2 variants

The aim of the work was to study the features of the infectious process in the lungs of animals used as models for assessing SARS-CoV-2 pathogenicity.Materials and methods. The strain of SARS-CoV-2 alpha variant virus was used in the work. The experiments were carried out on linear and transgenic mice, Syrian hamsters, guinea pigs, ferrets and two types of primates: rhesus macaques and green monkey. The pathomorphological examination was performed by optical microscopy of histological lung preparations using a computerized microscope with digital microphotography.Results and discussion. A comparative histological analysis of the lungs in six different types of laboratory animals was carried out when modeling a new coronavirus infection; similar morphometric signs of the severity of the disease caused by the SARS-CoV-2 virus in sensitive animals were determined, and a dose-dependent correlation of pathological changes in lung tissues with intranasal administration of various infectious doses was revealed. The features of pathomorphological changes in six different animal species in the simulation of a new coronavirus infection have been characterized, and their dose-dependent nature determined. The presented research results can be used to select a model animal for the purpose of in-depth study of the pathogenesis of COVID-19 caused by newly isolated coronavirus variants, the dynamics of immune reactions of the body during the development of the disease, as well as in vivo studies of the protective effect of promising therapeutic drugs and vaccines.

A system for obtaining recombinant variants of the Sendai virus of the Moscow strain carrying transgenes of protectively significant proteins of infectious agents was designed. On its basis, the Sen-RBDdelta(M) variant was obtained, expressing the secreted form of the SARS-CoV-2 S-protein receptor-binding domain, which showed immunogenicity and protection against SARS-CoV-2 in the BALB/c mouse model after a single intranasal injection.

INTRODUCTION:Intranasal vaccination using live vector vaccines based on non-pathogenic or slightly pathogenic viruses is the one of the most convenient, safe and effective ways to prevent respiratory infections, including COVID-19. Sendai virus is the best suited for this purpose, since it is respiratory virus and is capable of limited replication in human bronchial epithelial cells without causing disease. The aim of the work is to design and study the vaccine properties of recombinant Sendai virus, Moscow strain, expressing secreted receptor-binding domain of SARS-CoV-2 Delta strain S protein (RBDdelta) during a single intranasal immunization.MATERIALS AND METHODS:Recombinant Sendai virus carrying insertion of RBDdelta transgene between P and M genes was constructed using reverse genetics and synthetic biology methods. Expression of RBDdelta was analyzed by Western blot. Vaccine properties were studied in two models: Syrian hamsters and BALB/c mice. Immunogenicity was evaluated by ELISA and virus-neutralization assays. Protectiveness was assessed by quantitation of SARS-CoV-2 RNA in RT-PCR and histological analysis of the lungs.RESULTS:Based on Sendai virus Moscow strain, a recombinant Sen-RBDdelta(M) was constructed that expressed a secreted RBDdelta immunologically identical to natural SARS-CoV-2 protein. A single intranasal administration of Sen-RBDdelta(M) to hamsters and mice significantly, by 15 and 107 times, respectively, reduced replicative activity of SARS-CoV-2 in lungs of animals, preventing the development of pneumonia. An effective induction of virus-neutralizing antibodies has also been demonstrated in mice.CONCLUSION:Sen-RBDdelta(M) is a promising vaccine construct against SARS-CoV-2 infection and has a protective properties even after a single intranasal introduction.

INTRODUCTION:The COVID-19 pandemic combined with seasonal epidemics of respiratory viral diseases requires targeted antiviral prophylaxis with restorative and immunostimulant drugs. The compounds of natural origin are low-toxic, but active against several viruses at the same time. One of the most famous compounds is Inonotus obliquus aqueous extract. The fruit body of basidial fungus I. obliquus is called Chaga mushroom. The aim of the work ‒ was to study the antiviral activity of I. obliquus aqueous extract against the SARS-CoV-2 virus in vivo. MATERIALS AND METHODS:Antiviral activity of I. obliquus aqueous extract sample (#20-17) was analyzed against strain of SARS-CoV-2 Omicron ВА.5.2 virus. The experiments were carried out in BALB/c inbred mice. The SARS-CoV-2 viral load was measured using quantitative real-time PCR combined with reverse transcription. The severity of lung tissue damage was assessed by histological methods. RESULTS:The peak values of the viral load in murine lung tissues were determined 72 hours after intranasal inoculation at dose of 2,85 lg TCID50. The quantitative real-time PCR testing has shown a significant decrease in the viral load compared to the control group by 4,65 lg copies/ml and 5,72 lg copies/ml in the lung tissue and nasal cavity samples, respectively. Histological methods revealed that the decrease in the number and frequency of observed pathomorphological changes in murine lung tissues depended on the introduction of the compound under study. CONCLUSION:The results obtained indicate the possibility of using basidial fungus Inonotus obliquus aqueous extract as a preventive agent against circulating variants of SARS-CoV-2 virus.

As a result of this work, it was found that immunization with the experimental DNA vaccine pVAXrbd using jet injection significantly enhances the immune response of BALB/c mice. There was a tendency for specific antibody titers to increase with increasing vaccine dose. Challenge study showed that the vaccine has a dose-dependent protective effect, significantly reducing the viral load in lung tissues compared to the control.

In this research, the immunogenic and protective properties of the T-cell polyepitope immunogen BSI-CoV-Ub were investigated. The developed DNA construct induces a high level of cellular immune response and provides protective immunity against the Gamma variant of SARS-CoV-2 virus.

The aim of the work was to study the pathogenicity of newly emerging variants of SARS-CoV-2 on the model of the Syrian golden hamster.Materials and methods. We used the strains of SARS-CoV-2 virus related to the VOC circulating in the territory of the Russian Federation. The experiments were carried out on outbreed Syrian hamsters obtained from the nursery of the SSC VB “Vector”. The infectious titer of coronavirus in tissue samples collected from infected laboratory animals was determined on a Vero E6 cell culture. The Ct in RT-PCR was considered an additional parameter for monitoring the viral load in the samples. The severity of lung tissue damage in Syrian hamsters with COVID-19 was assessed by histological preparations.Results and discussion. 50 % infecting doses in case of the intranasal infection have been determined, histological analysis of lung tissues performed. The pathogenicity of various variants of the SARS-CoV-2 virus for the Syrian hamster has been evaluated, differences in infecting doses and pathological changes in the lungs have been revealed. SARS-CoV-2 viruses belonging to Beta genetic variant have the highest virulence, while Alpha variant has the lowest one when comparing the studied strains by the ID50 value. The Delta and Omicron variants have a matched ability to cause specific damage to the tissues of the respiratory tract, while being inferior only to the Beta variant. It has been demonstrated that Syrian hamsters are an adequate model for assessing the pathogenicity of the SARS-CoV-2 virus variants of concern. Variants of SARS-CoV-2 virus during intranasal infection has shown different degree of pathogenicity in the Syrian hamster model.

The aim of the research was to assess the susceptibility of mice of different lines to newly emerging variants of SARS-CoV-2.Materials and methods. The SARS-CoV-2 virus strains belonging to variants of concern (VOC) circulating in the territory of the Russian Federation were used in the study. Experiments involved three inbred mouse lines (BALB/c, CBA and C57Bl/6z) and CD1 outbred mice taken from the nursery of the SSC VB “Vector” of the Rospotrebnadzor. The infectious titer of coronavirus in tissue samples obtained from the laboratory animals was determined on a Vero E6 cell culture. The (Ct) threshold value in RT-PCR was considered an additional parameter for monitoring the viral load in the samples. The severity of lung tissue damage was assessed using histological preparations.Results and discussion. The susceptibility of various mouse lines to the genetic variant Beta of the SARS-CoV-2 virus has been investigated. During intranasal infection of the inbred and outbred mice with strains of VOC at a dose of 2·103 TCID50, the virus replicated in the lungs with maximum concentrations 72 hours after infection. The pathogenicity of genetic variants of the SARS-CoV-2 virus for BALB/c mice has been assessed, a 50 % infectious dose for intranasal infection (ID50) determined. Histological analysis showed COVID-19-specific lung tissue lesions in infected animals. Our study proves that BALB/c mice can be used as a model animal in screening studies when evaluating the effectiveness of therapeutic, vaccine preparations and studying the pathogenesis caused by VOC of the SARS-CoV-2 virus: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Omicron (B.1.1.529) and the like.