ABSTRACT
Interferons (IFN) have antiviral activity against many viruses, including SARS-CoV-2. A combination of IFN-a2b and the antioxidant taurine is widely used in the Russian Federation, and its antiviral activity has not been studied before. The aim of this study was to determine the antiviral activity of interferon drugs, in combination with taurine and without it. The study included cytotoxicity and antiviral activity assays of IFN-a2b preparations, when stored according to the instructions at 2-8degreeC, and after 1 month storage at the temperature of 20-26degreeC in a pre-opened state. The combination of IFN alpha-2b with taurine has a higher antiviral activity compared to IFN alpha-2b mono-preparation by more than 25% at a <<low>> and 85% at a <<high>> multiplicity of infection. Selectivity index for combinations of IFN-a2b (50,000 IU/dose) + taurine (1 mg/ml) and IFN-a2b (10,000 IU/ml) + taurine (0.8 mg/ml) was more than 600 units, whereas for the IFN-a2b (10,000 IU/ml) it was 200 units. Antiviral activity does not change after one month at room temperature. The combination of interferon with taurine at high concentrations was less toxic than interferon. The results obtained demonstrate practicability of interferon alpha-2b and taurine combination use for treatment and prevention of COVID-19.Copyright © Team of Authors, 2022.
ABSTRACT
Lactoferrin, artemisinin, and azithromycin exhibit a broad spectrum of antiviral, immunomodulatory, and anti-inflammatory effects. The experiments show that these drugs partially inhibit the infection caused by SARS-CoV-2 in vitro. This allows us to conclude that the effects on the entry of virions into cells mediated by each of these substances taken separately are insufficient for complete inhibition of the SARS-CoV-2 infection. The study was aimed to perform in vitro assessment of cytotoxicity and antiviral activity against the laboratory SARS-CoV-2 strain of the mixture of active ingredients: lactoferrin, artemisinin, and azithromycin. We used the Vero CCL81 (ATСС) cell line and the Dubrovka laboratory strain of SARS-CoV-2 (GenBank ID: MW161041.1), isolated in the Vero CCL81 cell culture from the nasopharyngeal swab of patient with СOVID-19. Cytotoxic effects and antiviral activity against SARS-CoV-2 of the drug mixture were assessed based on the cytopathic effects using the MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay. Hydroxychloroquine was used as a reference drug. It has been shown that at high (MOI 100) and low (MOI 20) multiplicity of infection used in the Vero CCL 81 cell culture, the mixture of artemisinin, lactoferrin and azithromycin has a significant effect on the SARS-CoV-2 reproduction, and IC50 (half maximal inhibitory concentration) is estimated as the 1: 2 dilution in both cases. The findings make it possible to conclude that the studied mixture is low toxic and shows significant antiviral effects in vitro. © 2022 Group of Companies Med Expert, LLC. All rights reserved.
ABSTRACT
INTRODUCTION: The variability of SARS-CoV-2 appeared to be higher than expected, the emergence of new variants raises concerns. The aim of the work was to compare the pathogenicity of the Wuhan and BA.1.1/Omicron variants in BALB/c mice and Syrian hamsters. MATERIALS AND METHODS: The study used strains of SARS-CoV-2: Dubrovka phylogenetically close to Wuhan-Hu-1, and LIA phylogenetically close to Omicron, BALB/c mice, transgenic mice B6.Cg-Tg(K18-ACE2)2Prlmn/HEMI Hemizygous for Tg(K18-ACE2)2Prlmn, Syrian golden hamsters. Animals were infected intranasally, pathogenicity was estimated by a complex of clinical, pathomorphological and virological methods. RESULTS: Comparative studies of SARS-CoV-2 Dubrovka and LIA strains on animal models demonstrated their heterogeneous pathogenicity. In parallel infection of BALB/c mice with Dubrovka and LIA variants, the infection proceeded without serious clinical signs and lung damage. Infection with the LIA strain resulted to a systemic disease with a high concentration of viral RNA in the lungs and brain tissues of animals. The presence of viral RNA in mice infected with the Dubrovka strain was transient and undetectable in the lungs by day 7 post-infection. Unlike the mouse model, in hamsters, the Dubrovka strain had a greater pathogenicity than the LIA strain. In hamsters infected with the Dubrovka strain lung lesions were more significant, and the virus spread through organs, in particular in brain tissue, was observed. In hamsters infected with the LIA strain virus was not detected in brain tissue. CONCLUSION: The study of various variants of SARS-CoV-2 in species initially unsusceptible to SARS-CoV-2 infection is important for monitoring zoonotic reservoirs that increase the risk of spread of new variants in humans.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cricetinae , Mice , Angiotensin-Converting Enzyme 2 , Disease Models, Animal , Mice, Inbred BALB C , RNA, Viral/genetics , SARS-CoV-2/geneticsABSTRACT
Interferons (IFN) have antiviral activity against many viruses, including SARS-CoV-2. A combination of IFN-a2b and the antioxidant taurine is widely used in the Russian Federation, and its antiviral activity has not been studied before. The aim of this study was to determine the antiviral activity of interferon drugs, in combination with taurine and without it. The study included cytotoxicity and antiviral activity assays of IFN-a2b preparations, when stored according to the instructions at 2-8°C, and after 1 month storage at the temperature of 20-26°C in a pre-opened state. The combination of IFN alpha-2b with taurine has a higher antiviral activity compared to IFN alpha-2b mono-preparation by more than 25% at a «low» and 85% at a «high» multiplicity of infection. Selectivity index for combinations of IFN-a2b (50,000 IU/dose) + taurine (1 mg/ml) and IFN-a2b (10,000 IU/ml) + taurine (0.8 mg/ml) was more than 600 units, whereas for the IFN-a2b (10,000 IU/ml) it was 200 units. Antiviral activity does not change after one month at room temperature. The combination of interferon with taurine at high concentrations was less toxic than interferon. The results obtained demonstrate practicability of interferon alpha-2b and taurine combination use for treatment and prevention of COVID-19.
ABSTRACT
One of the most important steps in the development of drugs and vaccines against a new coronavirus infection is their testing on a relevant animal model. The laboratory mouse, with well-studied immunology, is the preferred mammalian model in experimental medicine. However, mice are not susceptible to infection with SARS-CoV-2 due to the lack of human angiotensin-converting enzyme (hACE2), which is the cell receptor of SARS-CoV-2 and necessary for the entry of the virus into the cell. In present work, it was shown that intranasal administration of the adeno-associated vectors AAV9 and AAV-DJ encoding the hACE2 provided a high level of expression of ACE2 gene in the lungs of mice. In contrast, the introduction of the AAV6 vector led to a low level ACE2 expression. Infection with SARS-CoV-2 of mice expressing hACE2 in the lungs led to virus replication and development of bronchopneumonia on the 7th day after infection. Thus, a simple method for delivering the human ACE2 gene to mouse lungs by intranasal administration of the AAV vector has been proposed. This approach enabled rapid generation of mouse model for studying coronavirus infection.
ABSTRACT
Introduction.The COVID-19 pandcmic has stimulated the search for drugs with specific antiviral activity against the new pathogenic strain of the SARS-CoV-2 coronavirus. First of all, scientific search was aimed at studying drugs with already proven efficacy against influenza and ARVI. The aim of this worfc was to study the antiviral activity of Cytovir∗-3 in vitro in relation to the cytopathogenic effect of the SARS-CoV-2 virus. Material and methods. The antiviral activity of the drug Cy- tovir∗-3 against the SABS-CoV-2 virus was studied in experimental models in vitro on Vero CCL81 cell culture (ATCC).The maximum tolerated concentration and the 50% cytotoxic dose were determined using a quantitative microculture tetra- zolium test assay to calculate the working range of the concentrations of the test drug. Results and discussion. As a result of the study, it was shown that the greatest activity of the drug was manifested when it was added to the cells 24 hours before and 1 hour and 24 hours after viral infection, the inhibition level reached 53% (>IC50) at the drug concentrations of 105,55, and 85 fig/ml, respectively. Cytovir∗-3 suppressed the viral activity of SARS-CoV-2 in the dose range from 10 pg/ml to 105 pg/ml under the indicated infection conditions. It was found that the drug did not exhibit cytotoxic effects on the Vero cell culture in the range of antiviral doses. Conclusion. The antiviral activity of Cytovir∗-3 against the SARS-CoV-2 virus has been proven due to the achievement of IC50, which is below the maximum tolerated dose of 149 pg/ml.
ABSTRACT
On account of the COVID-19 pandemic, the global pharmaceutical industry has achieved impressive results in the development and introduction of various types of vaccines causing the formation of acquired immunityagainst the SARS-CoV-2 coronavirus Into clinical practice. However, none of them currently show the declared one hundred percent guarantee of protection. In the case of the COVID-19 disease, patients with concomitant pathologies are the most vulnerable to the occurrence of severe complications. The aerosol route of transmission of SARS-CoV-2 contributes to the emergence of outbreaks of the new coronavirus infection in crowded places and closed rooms with poor ventilation. In this regard, an urgent problem is the search for drugs with local antiviral activity, which, together with restrictive measures and mask wearing policy, can potentially reduce the likelihood of contracting coronavirus. In this experimental in vitro study on Vero CCL81 cell culture (ATCC), the local anti¬viral activity of the drugThymogen∗ spray against the SARS-CoV-2 virus was studied in comparison with the antiseptic Miramistin® solution. As a result of the experiment, no toxic effects on Vero ceils were detected in the drugs in the studied concentrations. In a series of experiments, Thymogen∗ spray showed local antiviral activity against SARS-CoV-2 when the virus titer was 5,2 lg TCID50. Therefore, the drugThymogen® dosed nasal spray has high potential as a topical drug for prevention and treatment of COVID-19 disease, which requires additional confirmation in relevant clinical studies. © 2021 Media Sphera Publishing Group. All rights reserved.
ABSTRACT
Introduction. In clinical practice, the differential diagnosis of COVID-19 can be challenging during the flu season, entailing serious consequences such as delays in appropriate control measures against the SARS-CoV-2 pandemic. Another problem is posed by co-infection of SARS-CoV-2 and influenza virus (IV), which significantly contributes to the severity of the COVID-19 disease. This study was aimed to explore the cross-impact of co-administration of Russian influenza and COVID-19 vaccines on development of specific immunity in laboratory animals. Materials and methods. The study was conducted on BALB/c mice. The animals were inoculated intramuscularly with the vaccine for COVID-19 prevention (CoviVac) and the vaccine for influenza prevention (Flu-M). The sera from the immunized animals were examined separately. Three IV strains were used in the hemagglutination inhibition assay. Antibodies (Abs) against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA). The neutralization test was performed to detect virus neutralizing antibodies against SARS-CoV-2 and IV. Results. Relatively high titers of specific Abs were found in the groups of animals inoculated with one vaccine and with two vaccines concurrently. In the groups of animals inoculated with CoviVac and with two vaccines concurrently, both in the ELISA test and in the neutralization test, the average titers of specific Abs against SARSCoV-2 did not demonstrate any statistical difference. The group of animals inoculated concurrently with two vaccines demonstrated statistically higher titers of Abs against IV after the second immunization compared to the group of animals inoculated with Flu-M. Discussion. The study has shown that post-vaccination immunity both to IV and to SARS-CoV-2 develops after co-vaccination with two vaccines. The observed enhanced post-vaccination immune response to IV in the coimmunized laboratory animals needs further research. Conclusion. The performed studies suggest the possibility of co-administration of two vaccines to prevent influenza and COVID-19. © 2021, Central Research Institute for Epidemiology. All rights reserved.