ABSTRACT
OBJECTIVE AND DESIGN: The existing biological models of diffuse alveolar damage (DAD) in mice have many shortcomings. To offset these shortcomings, we have proposed a simple, nonsurgical, and reproducible method of unilateral total damage of the left lung in ICR mice. This model is based on the intrabronchial administration of a mixture of bacterial lipopolysaccharide (LPS) from the cell wall of S. enterica and α-galactosylceramide (inducing substances) to the left lung. METHODS: Using computer tomography of the lungs with endobronchial administration of contrast material, we have been able to perform an operative intravital verification of the targeted delivery of the inducer. The model presented is characterized by more serious and homogeneous damage of the affected lung compared to the existing models of focal pneumonia; at the same time, our model is characterized by longer animal survival since the right lung remains intact. RESULTS: The model is also characterized by diffuse alveolar damage of the left lung, animal survival of 100%, abrupt increases in plasma levels of TNFa, INFg, and IL-6, and significant myocardial overload in the right heart. It can be used to assess the efficacy of innovative drugs for the treatment of DAD and ARDS as the clinical manifestations that are developed in patients infected with SARS-CoV-2. Morphological patterns of lungs in the noninfectious ("sterile") model of DAD induced by LPS simultaneously with α-galactosylceramide (presented here) and in the infectious model of DAD induced by SARS-CoV-2 have been compared. CONCLUSION: The DAD model we have proposed can be widely used for studying the efficacy of candidate molecules for the treatment of infectious respiratory diseases, such as viral pneumonias of different etiology, including SARS-CoV-2.
Subject(s)
COVID-19 , Pneumonia, Viral , Animals , Disease Models, Animal , Humans , Lipopolysaccharides , Lung , Mice , Mice, Inbred ICR , SARS-CoV-2ABSTRACT
INTRODUCTION: The pandemic spread of a new coronavirus infection, COVID-19, has caused a global emergency and attracted the attention of public health professionals and the population of all countries. A significant increase in the number of new cases of SARS-CoV-2 infection demonstrates the urgency of finding drugs effective against this pathogen.The aim of this work was to evaluate the in vitro antiviral efficacy of human recombinant alpha-2b interferon (IFN-α2b) against SARS-CoV-2 virus. MATERIAL AND METHODS: The experiments had been carried out on Vero Cl008, the continuous line of African green monkey (Chlorocebus sabaeus) kidney cells. The effectiveness of the drugs was assessed by the suppression of viral reproduction in vitro. The biological activity was determined using titration of a virus-containing suspension in a Vero Cl008 cell culture by the formation of negative colonies. RESULTS: The antiviral efficacy of the IFN-α2b-based medications, which have a high safety profile and proven efficacy in the prevention and treatment of influenza and acute respiratory viral infections (ARVI), has been studied against the new pandemic SARS-CoV-2 virus in vitro experiments in Vero C1008 cell culture. IFN-α2b effectively inhibits the reproduction of the virus when applied both 24 hrs before and 2 hrs after infection. In the IFN-α2b concentration range 102-106 IU/ml a complete suppression of the reproduction of the SARS-CoV-2 virus had been demonstrated. DISCUSSION: IFN-α2b demonstrated in vitro high antiviral activity against SARS-CoV-2. In addition, the substance has a high chemotherapeutic index (>1000). CONCLUSION: Medications for intranasal use based on IFN-α2b have high antiviral activity and are promising drugs for in vivo study in terms of prevention and treatment of COVID-19.
Subject(s)
COVID-19 Drug Treatment , COVID-19/immunology , Interferon alpha-2/pharmacology , SARS-CoV-2/immunology , Animals , COVID-19/pathology , Chlorocebus aethiops , Humans , Vero CellsABSTRACT
The comparative study of the therapeutic efficacy of Triazavirin against experimental Forest-Spring encephalitis on albino mice vs. the active drug Ribavirin® showed that in high doses (200-400 mg/kg) Triazavirin moderately protected the infected animals. A significant increase of the animal lifespan in the test groups (from 4.1 to 4.8 days) and a statistically (p ≤ 0.05) valid decrease of the virus accumulation in the target organ (the brain) were observed.
Subject(s)
Antiviral Agents/pharmacology , Azoles/pharmacology , Encephalitis Viruses, Tick-Borne/drug effects , Encephalitis, Tick-Borne/drug therapy , Triazines/pharmacology , Virus Replication/drug effects , Animals , Brain/drug effects , Brain/pathology , Brain/virology , Encephalitis Viruses, Tick-Borne/pathogenicity , Encephalitis Viruses, Tick-Borne/physiology , Encephalitis, Tick-Borne/mortality , Encephalitis, Tick-Borne/pathology , Encephalitis, Tick-Borne/virology , Mice , Ribavirin/pharmacology , Survival Analysis , Treatment Outcome , Triazoles , Viral Load/drug effectsABSTRACT
Prophylactic efficacy of Triazavirin against experimental Forest-Spring encephalitis was studied on albino mice. vs. the active drug Ribavirin. A significant increase of the animal lifespan in the test groups (from 4 to 5 days) and a statistically (p < or = 0.05) valid decrease of the virus accumulation level in the target organ (the brain) were observed.
Subject(s)
Azoles/pharmacology , Encephalitis, Tick-Borne/prevention & control , Triazines/pharmacology , Animals , Brain/metabolism , Brain/pathology , Brain/virology , Cell Line , Disease Models, Animal , Encephalitis, Tick-Borne/metabolism , Encephalitis, Tick-Borne/pathology , Mice , Swine , TriazolesABSTRACT
High in vitro and in vivo efficacy of Ingavirin against the Mexican pandemic influenza virus A/H1N1/2009, strains A/California/04/2009 (H1N1) and A/California/07/2009 (H1N1) vs. the reference drug Arbidol was studied and verified when used therapeutically and prophylactically.
