ABSTRACT
INTRODUCTION: Influenza is one of the most pressing global health problems. Despite the wide range of available anti-influenza drugs, the viral drug resistance is an increasing concern and requires the search for new approaches to overcome it. A promising solution is the development of drugs with action that is based on the inhibition of the activity of cellular genes through RNA interference. AIM: Evaluation in vivo of the preventive potential of miRNAs directed to the cellular genes FLT4, Nup98 and Nup205 against influenza infection. MATERIALS AND METHODS: The A/California/7/09 strain of influenza virus (H1N1) and BALB/c mice were used in the study. The administration of siRNA and experimental infection of animals were performed intranasally. The results of the experiment were analyzed using molecular genetic and virological methods. RESULTS: The use of siRNA complexes Nup98.1 and Nup205.1 led to a significant decrease in viral reproduction and concentration of viral RNA on the 3rd day after infection. When two siRNA complexes (Nup98.1 and Nup205.1) were administered simultaneously, a significant decrease in viral titer and concentration of viral RNA was also noted compared with the control groups. CONCLUSIONS: The use of siRNAs in vivo can lead to an antiviral effect when the activity of single or several cellular genes is suppressed. The results indicate that the use of siRNAs targeting the cellular genes whose expression products are involved in viral reproduction is one of the promising methods for the prevention and treatment of not only influenza, but also other respiratory infections.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza, Human , Orthomyxoviridae Infections , Animals , Mice , Humans , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/metabolism , Cell Line , Antiviral Agents/pharmacology , RNA, Viral , Reproduction , Orthomyxoviridae Infections/genetics , Orthomyxoviridae Infections/prevention & control , Virus ReplicationABSTRACT
Vaccination against COVID-19 is the most effective method of controlling the spread of SARS-CoV-2 and reducing mortality from this disease. The development of vaccines with high protective activity against a wide range of SARS-CoV-2 antigenic variants remains relevant. In this regard, evaluation of the effectiveness of physical methods of virus inactivation, such as ultraviolet irradiation (UV) of the virus stock, remains relevant. This study demonstrates that the UV treatment of SARS-CoV-2 completely inactivates its infectivity while preserving its morphology, antigenic properties, and ability to induce the production of virus-neutralizing antibodies in mice through immunization. Thus, the UV inactivation of SARS-CoV-2 makes it possible to obtain viral material similar in its antigenic and immunogenic properties to the native antigen, which can be used both for the development of diagnostic test systems and for the development of an inactivated vaccine against COVID-19.
Subject(s)
COVID-19 , Viral Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Ultraviolet Rays , Vaccines, InactivatedABSTRACT
Effects of a new synthetic progesterone derivative 17a-acetoxy-3b-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (ABMP) and the reference gestagen preparations on the rat thymus were evaluated by the degree of variation of the intracellular levels of calcium and cAMP, 3H-uridine inclusion into RNA, thymocyte viability, and thymus mass. It is shown that gestagens can produce antiglucocorticoid action on thymocytes, this activity being most pronounced in the case of ABMP.
Subject(s)
17-alpha-Hydroxyprogesterone/analogs & derivatives , Antineoplastic Agents/pharmacology , Progestins/pharmacology , Receptors, Glucocorticoid/antagonists & inhibitors , T-Lymphocytes/drug effects , 17-alpha-Hydroxyprogesterone/adverse effects , 17-alpha-Hydroxyprogesterone/pharmacology , Animals , Antineoplastic Agents/adverse effects , Apoptosis , Calcium/metabolism , Cell Survival/drug effects , Cyclic AMP/metabolism , Dexamethasone/pharmacology , Female , In Vitro Techniques , Progestins/adverse effects , Rats , Receptors, Glucocorticoid/metabolism , T-Lymphocytes/physiology , Thymus Gland/cytology , Transcription, GeneticABSTRACT
The combined cytostatic effect of doxorubicin and gestagens progesterone, medroxyprogesterone acetate, mecigestone, and butagest on doxorubicin-resistant and doxorubicin-sensitive human breast cancer MCF-7 cells was studied by the MTT assay. On the 6th day of incubation progesterone, medroxyprogesterone acetate, mecigestone, and butagest in high concentrations (10(-5) M) potentiated the cytostatic action of doxorubicin in sensitive and resistant cells by 30-50%. Potentiation of the cytostatic effect produced by doxorubicin in sensitive cells is related to intrinsic cytotoxic activity of gestagens. In resistant cells these changes are associated with potentiation of the effect of doxorubicin.
