Free radical reactions play an important role in biological functions of living systems. The balance between oxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Experimental works demonstrate the role of oxidative stress that is caused by influenza virus as well as the toxic effects of some antiviral drugs. Therefore, antiviral drugs should be characterized by its pro- and antioxidant activity, because it can affect its therapeutic efficiency. The aim of the study was to quantify the antioxidant capacity and propose the mechanism of the antioxidant effect of the antiviral drug Umifenovir (Arbidol®). The kinetic chemiluminescence with the 2,2’-azobis (2-amidinopropane) dihydrochloride + luminol system was used to quantify the antioxidant capacity of Umifenovir relative to the standard compound Trolox. With computer simulation, the reaction scheme and rate constants were proposed. The antioxidant capacity of 0.9 μM Umifenovir (maximum concentration of Umifenovir in blood after oral administration of 200 mg) was as high as 1.65 ± 0.18 μM of Trolox. Thus, the total antioxidant capacity of Umifenovir is comparable to the antioxidant capacity of Trolox. Unlike Trolox, Umifenovir reacts with free radicals in two stages. For Trolox, the free radical scavenging rate constant was k = 2000 nM−1 min.−1, for Umifenovir k1 = 300 nM−1min.−1, k2 = 4 nM−1min.−1. Slower kinetics of Umifenovir provides the prolonged antioxidant effect when compared to Trolox. This phenomenon can make a serious contribution to the compensation of oxidative stress that is caused by a viral disease and the therapeutic effect of the drug.
An escalating pandemic of the novel SARS-CoV-2 virus is impacting global health, and effective antivirals are needed. Umifenovir (Arbidol) is an indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It has been shown that umifenovir has broad spectrum activity against different viruses. We evaluated the sensitivity of different coronaviruses, including the novel SARS-CoV-2 virus, to umifenovir using in vitro assays. Using a plaque assay, we revealed an antiviral effect of umifenovir against seasonal HCoV-229E and HCoV-OC43 coronaviruses in Vero E6 cells, with estimated 50% effective concentrations (EC50) of 10.0 ± 0.5 µM and 9.0 ± 0.4 µM, respectively. Umifenovir at 90 µM significantly suppressed plaque formation in CMK-AH-1 cells infected with SARS-CoV. Umifenovir also inhibited the replication of SARS-CoV-2 virus, with EC50 values ranging from 15.37 ± 3.6 to 28.0 ± 1.0 µM. In addition, 21–36 µM of umifenovir significantly suppressed SARS-CoV-2 virus titers (≥2 log TCID50/mL) in the first 24 h after infection. Repurposing of antiviral drugs is very helpful in fighting COVID-19. A safe, pan-antiviral drug such as umifenovir could be extremely beneficial in combating the early stages of a viral pandemic.
1 February 2015 in Journal of the Marine Biological Association of the United Kingdom
The degree of development and operability of the indicators for the Marine Strategy Framework Directive (MSFD) using Descriptor 1 (D1) Biological Diversity was assessed. To this end, an overview of the relevance and degree of operability of the underlying parameters across 20 European countries was compiled by analysing national directives, legislation, regulations, and publicly available reports. Marked differences were found between countries in the degree of ecological relevance as well as in the degree of implementation and operability of the parameters chosen to indicate biological diversity. The best scoring EU countries were France, Germany, Greece and Spain, while the worst scoring countries were Italy and Slovenia. No country achieved maximum scores for the implementation of MSFD D1. The non-EU countries Norway and Turkey score as highly as the top-scoring EU countries. On the positive side, the chosen parameters for D1 indicators were generally identified as being an ecologically relevant reflection of Biological Diversity. On the negative side however, less than half of the chosen parameters are currently operational. It appears that at a pan-European level, no consistent and harmonized approach currently exists for the description and assessment of marine biological diversity. The implementation of the MSFD Descriptor 1 for Europe as a whole can therefore at best be marked as moderately successful.
Introduction: Evaluation of anti-inflammatory action of Codelac® Broncho with Thymus Serpyllum (elixir) in comparison with Fenspiride was carried out on the model of acute carrageenan inflammation of the paws in rats. Materials and methods: Edema was caused by subplantar injection of 0.1 ml of 1% λ- carrageenan gel into the hind paw. The severity of edema was assessed by using 37140 plethysmometer (UGO BASILE, Italy). The measurements were performed before edema induction and 1, 2, 4, 12, 24, 48, 72, 96 and 120 hours afterwards. Anti-inflammatory activity of the drugs was also evaluated based on the analysis of rats’ blood, C-reactive protein concentration and histological examination results. Results and discussion: A decrease in the paw volume increment was revealed in the group with the studied drug in comparison with the group with the carrageenan edema model (control) 4, 12, 24 hours after injection of carrageenan (p<0.05). As a result of plethysmometry, a more pronounced anti-inflammatory effect of the studied drug than that of Fenspiride was revealed. There was a significant decrease in the levels of leukocytes (p<0.05), lymphocytes (p<0.05), monocytes (p<0.05) and neutrophils (p<0.05) in the group with the studied drug compared to those the the control 48 hours after the initiation of edema, while in the group with Fenspiride, there was only a decrease in the levels of leukocytes (p<0.05) and lymphocytes (p<0.05). There were no differences in the concentration of C-reactive protein between the groups. Conclusion: The obtained data indicate a more pronounced anti-inflammatory activity of Codelac® Broncho with Thymus Serpyllum in comparison with Fenspiride, on the model of acute carrageenan inflammation of the paw in rats.