Antiviral Activity of Kagocel&lt;sup&gt;®&lt;/sup&gt; in vitro Against Virus SARS-CoV-2

Loginova, S. Ya.; Щукина, В Н; Savenko, S. V.; Борисевич, С. В.

doi:10.37489/0235-2990-2020-65-3-4-3-6

Cited by 8 publications

(2 citation statements)

References 11 publications

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“…The experiments were conducted under the conditions of a specialized BSL-3 laboratory (Sergiev Posad). In the mice that died during the follow-up period, the levels of SARS-CoV-2 accumulation in the lungs were assessed based on the formation of negative colonies (PFU) in the cultured Vero Cl008 cells [ 21 ]. After a two-week inactivation period in 10% formalin solution, the lungs were subjected to histological examination.…”

Section: Methodsmentioning

confidence: 99%

A new mouse unilateral model of diffuse alveolar damage of the lung

et al. 2022

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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.

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Section: Methodsmentioning

confidence: 99%

A new mouse unilateral model of diffuse alveolar damage of the lung

et al. 2022

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“…Clinical data corroborate the efficacy of kagocel for influenza treatment ( Fazylov et al, 2016 ; Sologub and Tsvetkov, 2017 ) and for fighting other viral infections ( Galegov et al, 2002 ; Loginova et al, 2020 ) as a monotherapy or a part of a combination treatment ( Popov et al, 2017b ). Analysis of interferon concentrations in plasma of patients with influenza evidence increased cytokine levels upon kagocel administration ( Popov et al, 2017a ).…”

Section: Introductionmentioning

confidence: 72%

Gene Expression Pattern of Peyer’s Patch Lymphocytes Exposed to Kagocel Suggests Pattern-Recognition Receptors Mediate Its Action

et al. 2021

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Kagocel is a synthetic carboxymethylcellulose derivative copolymerized with gossypol. Clinical data evidence its safety and efficiency for the treatment of flu and other viral infections via enhancement of interferon production. The gut-associated lymphoid tissue seems a likely site of kagocel action. The study was aimed to investigate the molecular mechanisms of its action using murine Peyer’s patches lymphocytes as a test system and the cytokines production and gene expression patterns as the primary outcomes. The Peyer’s patches lymphocytes isolated from BALB/c mice were stimulated with concanavalin A, or, to mimic viral infection, with a combination of concanavalin A and TLR3 ligand poly I:C. After 24 h of stimulation the cells were treated with saline, 30, 100, or 300 μg/ml of kagocel, or, as positive controls, 300 μg/ml oats b-D-glucan or 300 μg/ml lentinan. After 24 and 72 h of incubation with these drugs cytokines production was analyzed with ELISA and gene expression pattern was investigated using nCounter Inflammation panel chips followed by bioinformatics analysis. Expression of genes involved in the inflammatory response, antiviral defense, lymphocytes survival and proliferation (C1qa, C2, C3, Ccl21a, Il11, Il1b, Il23a, Il5, Ltb4r2, Alox15, Pla2g4a, Ptger1, Mapkapk5, Hras, Ifna1, Tlr2, Mrc1, Mx2) was upregulated in kagocel-treated Peyer’s patches lymphocytes. A list of plausible transcription factors (CEBPs, IRF, NFκB, RXR, Stat, Tead4, and ZSCAN) and master-regulators has been identified (cIAP, CIKS, dock9, MEKK1, FXR, IKK, IRAK, TRAF, dsRNA:TLR3:TRIF). The changes in gene expression pattern and the outcomes of bioinformatics analysis suggest that pattern recognition receptors, TLRs and dectin-1, are the key mediators of kagocel immunomodulatory action, with the possible involvement of interferon autocrine loop. The genes upregulated with kagocel include diverse components of the innate immune defense system.

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Clinical efficacy and antioxidant properties of interferon inducers in the treatment of acute respiratory diseases in children

Vakhitov,

Mamleev,

Vakhitova

2023

Medicinskij sovet

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Introduction. Diagnosis, treatment and prevention of respiratory infections in the practice of a pediatrician occupy one of the leading places. Currently, much attention is paid to various links in the pathogenesis of viral respiratory diseases. Among them, particular importance is attached to the system of antioxidant defense and cytokine regulation of inflammation. It is important to study the effect of various drugs on these links of pathogenesis in order to increase the clinical effectiveness of therapeutic methods.Aim. To evaluate the clinical efficacy and impact on lipid peroxidation of Kagocel® in the treatment of respiratory viral infections in children.Materials and methods. An observational study was conducted involving 124 children aged 6 to 15 years with manifestations of a respiratory viral infection who received symptomatic treatment, of which 89 children additionally took antiviral therapy with Kagocel®.Results. Along with the good tolerance of Kagocel® and the absence of side effects in children on the background of its use, a significantly shorter period of regression of the main clinical symptoms of acute respiratory infection was shown. It was noted that in children taking Kagocel® on the 3rd-5th day of therapy, there is an increase in the total antioxidant activity of blood plasma and a decrease in the level of malondialdehyde compared with patients who did not take the drug, which demonstrates the antioxidant effects of Kagocel®, which certainly have a positive effect on the character course of the healing process.Conclusion. Kagocel® has been shown to have high clinical efficacy and antioxidant effects.

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Antiviral Activity of Kagocel<sup>®</sup> in vitro Against Virus SARS-CoV-2

Cited by 8 publications

References 11 publications

A new mouse unilateral model of diffuse alveolar damage of the lung

A new mouse unilateral model of diffuse alveolar damage of the lung

Gene Expression Pattern of Peyer’s Patch Lymphocytes Exposed to Kagocel Suggests Pattern-Recognition Receptors Mediate Its Action

Clinical efficacy and antioxidant properties of interferon inducers in the treatment of acute respiratory diseases in children

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