Anti-viral activity of enisamium iodide against viruses of influenza and ARVI’s on different cell lines

Zarubaev, Vladimir V.; Slita, Alexander V.; Синегубова, Eкатерина O.; Мурылева, Анна А.; Лаврентьева, И. Н.

doi:10.26442/00403660.2020.11.000872

Cited by 3 publications

(2 citation statements)

References 21 publications

(20 reference statements)

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“…Moreover, unlike remdesivir, enisamium does not require intravenous administration, which would be advantageous for its use outside a hospital setting. Together with observations that enisamium can inhibit other RNA virus infections, and DNA virus infections [ 17 , 18 ], these results here suggest that it can act as a broad-spectrum polymerase inhibitor in vitro.…”

Section: Discussionsupporting

confidence: 83%

“…The cells were infected with SARS-CoV-2 at multiplicity of infection 0.01 for 1 h, and compound reapplied following virus removal. At 48 h post infection, the cytopathic effect was recorded by examination of the infected cultures by light microscopy and supernatant collected to quantify virus RNA by RT-qPCR as described previously, using nsp12-specific primers 5′-GTGARATGGTCATGTGTGGCGG-3′ and 5′-CARATGTTAAASACACTATTAGCATA-3′ [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Cells were fixed with acetone/methanol (40:60) and immunostained using a SARS-CoV-2 nucleoprotein monoclonal antibody (1:500, Sinobiological, Cat #40143-R019-100 µL).…”

Section: Methodsmentioning

confidence: 99%

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Enisamium Inhibits SARS-CoV-2 RNA Synthesis

et al. 2021

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Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called coronavirus disease 2019 (COVID-19). While control of the SARS-CoV-2 spread partly depends on vaccine-induced or naturally acquired protective herd immunity, antiviral strategies are still needed to manage COVID-19. Enisamium is an inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. In vitro, enisamium acts through metabolite VR17-04 and inhibits the activity of the influenza A virus RNA polymerase. Here we show that enisamium can inhibit coronavirus infections in NHBE and Caco-2 cells, and the activity of the SARS-CoV-2 RNA polymerase in vitro. Docking and molecular dynamics simulations provide insight into the mechanism of action and indicate that enisamium metabolite VR17-04 prevents GTP and UTP incorporation. Overall, these results suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis in vitro.

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Section: Discussionsupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Enisamium Inhibits SARS-CoV-2 RNA Synthesis

et al. 2021

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Enisamium Reduces Influenza Virus Shedding and Improves Patient Recovery by Inhibiting Viral RNA Polymerase Activity

Velthuis

Zubkova

Shaw

et al. 2021

Antimicrob Agents Chemother

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Infections with respiratory viruses constitute a huge burden on our health and economy. Antivirals against some respiratory viruses are available, but further options are urgently needed. Enisamium iodide (laboratory code FAV00A, trade name Amizon®) is an antiviral marketed in countries of the Commonwealth of Independent States for the treatment of viral respiratory infections, but its clinical efficacy and mode of action are not well understood. Here, we investigated the efficacy of enisamium in patients aged between 18-60 years with confirmed influenza and other viral respiratory infections. Enisamium treatment resulted in reduced influenza virus shedding (at day 3, 71.2% in enisamium group tested negative versus 25.0% in placebo group, p < 0.0001), faster patient recovery (at day 14, 93.9% in enisamium group had recovered versus 32.5% in placebo group, p < 0.0001), and reduced disease symptoms compared to placebo (from 9.6 ± 0.7 to 4.6 ± 0.9 score points in enisamium group versus 9.7 ± 1.1 to 5.6 ± 1.1 score points in placebo group, p < 0.0001). Using mass-spectrometry, and cell-based and cell-free viral RNA synthesis assays, we identified a hydroxylated metabolite of enisamium, VR17-04. VR17-04 is capable of inhibiting influenza virus RNA synthesis and present in plasma of patients treated with enisamium. VR17-04 inhibits the activity of the influenza virus RNA polymerase more potently than its parent compound. Overall, these results suggest that enisamium is metabolized in humans to an inhibitor of the influenza virus RNA polymerase that reduces viral shedding and improves patient recovery in influenza patients.

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The mechanisms of anti-inflammatory action of enisamium iodide

Федотчева

Semeikin

et al. 2022

Terapevticheskii arkhiv

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Aim. The role of cyclooxygenases (COX-1 and/or COX-2), transcription nuclear factor NF-B, anti-inflammatory cytokines TGF1b, IL-4, IL-10 and pro-inflammatory cytokines IL-1, IL-6 were studied to substantiate the expediency of antiviral agent enisamium iodide (Nobazit) using to regulate key inflammatory components in acute respiratory infections, IL-8, TNF-alpha in the realization of the pharmacological activity of this drug. Materials and methods. Gene expression was determined by real-time RT-PCR, the concentration of interleukins was determined by ELISA, and the viability of peripheral blood mononuclear cells (PBMC) was assessed by the MTT spectrophotometric method. The chemiluminescence method was used to assess PBMC oxidant activity. Results. Enisamium iodide (10 M) reduced mRNA levels of COX-1, COX-2, NF-B, TGF1b, IL-1, IL-6 in stimulated PBMC of healthy donors by an average of 48% (p0.05). At 5 times higher concentration, 50 M, enisamium iodide suppressed the expression of these genes by an average of 43% (p0.05). At a concentration of 100 M, enisamium iodide reduced the expression of COX-2, TGF1b, IL-1, IL-6 by an average of 47% (p0.05). At a concentration of 10 M, enisamium iodide stimulated the secretion of IL-10 by mononuclear cells by 1.2 times, p0.05. The tested drug at a concentration of 50 M did not affected on the concentration of IL-1, IL-4, IL-8 and TNF-alpha, but significantly stimulated the production of IL-10 by 1.5 times, p0.05. The chemiluminescence method revealed that enisamium iodide in the entire concentration range (10100 M) does not reduce the viability of macrophages, but inhibits their oxidative activity (maximum value of CL intensity) by an average of 55% (p0.05). Conclusion. The anti-inflammatory effect of enisamium iodide at a concentration of 10 M may be associated with inhibition of the expression of COX-1, 2, NF-B, IL-1, IL-6, TGF1b and an increase in the expression and production of IL-10. An additional contribution to the anti-inflammatory activity of enisamium iodide is made by its antioxidant and antiradical activity. The absence of the effect of enisamium iodide (10100 M) on the viability of PBMC indicates its safety for the cells of the immune system and the expediency of using it to suppress inflammatory reactions in acute respiratory infections, restore the quality of life of patients and the possibility of using Nobazit as an effective agent for treatment of these infections of various etiologies.

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Anti-viral activity of enisamium iodide against viruses of influenza and ARVI’s on different cell lines

Cited by 3 publications

References 21 publications

Enisamium Inhibits SARS-CoV-2 RNA Synthesis

Enisamium Inhibits SARS-CoV-2 RNA Synthesis

Enisamium Reduces Influenza Virus Shedding and Improves Patient Recovery by Inhibiting Viral RNA Polymerase Activity

The mechanisms of anti-inflammatory action of enisamium iodide

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