Umifenovir susceptibility monitoring and characterization of influenza viruses isolated during ARBITR clinical study

Leneva, I. A.; Фалынскова, И. Н.; Махмудова, Н. Р.; Поромов, А. А.; Yatsyshina, S. B.; Maleev, V V

doi:10.1002/jmv.25358

Cited by 29 publications

(26 citation statements)

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“…Mice with respiratory chain defects were highly susceptible to viral infection and exhibited significant lung inflammation [2]. Oxidative and nitrosative stress may also contribute to reduced All 18 clinical isolates of influenza A viruses that were obtained before and during therapy were susceptible to Umifenovir with 50% effective concentration ranging from 8.4 +/− 1.1 to 17.4 +/− 5.4 µM without the development of drug-resistant variants [22]. Experimental studies at concentrations of 25-100 mg/mL proved the direct antiviral activity of Umifenovir on the early viral replication of severe acute respiratory syndrome (SARS) virus in the cultured GMK-AH-1 cells [23].…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Potential of Antiviral Drug Umifenovir

et al. 2020

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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 k 1 = 300 nM −1 min. −1 , k 2 = 4 nM −1 min. −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.

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Section: Introductionmentioning

confidence: 99%

Antioxidant Potential of Antiviral Drug Umifenovir

et al. 2020

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“…Since COVID-19 has been pandemic, a variety of antiviral drugs have been investigated on patients with COVID-19 (12). Arbidol is a Russian antiviral drug that seems to be effective against many viruses including in uenza A, B, and C, respiratory syncytial virus (RSV), severe acute respiratory syndromerelated coronavirus (SARS-CoV), adenovirus, parain uenza, poliovirus, rhinovirus, coxsackievirus, zika virus, hepatitis B and C viruses (13)(14)(15). It has been demonstrated that Arbidol has a dual effect on cell attachment and replication, and thus a broad-spectrum effect on viruses (16,8), so it is administered for post-exposure prophylaxis and treatment (17).…”

Section: Discussionmentioning

confidence: 99%

Effect of Arbidol on COVID-19: A Randomized Controlled Trial

Nojomi

Yasin

Keyvani

et al. 2020

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Background: The treatment of patients with COVID-19 included supportive care to relief the symptoms mainly. Although WHO mentioned there is not any effective treatments for COVID-19, but there is some reporting about the use of some antiviral drugs. The aim of current study is to determine the effect of Arbidol (ARB) on COVID-19 disease. Methods: Using an open label randomized controlled trial, effectiveness of ARB on COVID-19 disease was conducted in a teaching hospital. One hundred eligible patients with diagnosis of Covid-19 recruited in the study and assigned randomly to two groups of either Hydroxychloroquine followed by Kaletra (Lopinavir-ritonavir) or Hydroxychloroquine followed by ARB. The primary outcome was hospitalization duration and clinical improvement 7 days after admission. The criteria of improvement were relief of cough, dyspnea and fever. Time to relieving fever was assessed across two groups too. Without any drop out, 100 patients were entered to final analysis with significant level of 0.05. Results: The mean age of the patients was 56.6 (17.8) and 56.2 (14.8) in ARB and Kaletra groups respectively. Majority of patients were male across two groups (66% and 54%). The duration of hospitalization in ARB group was less than Kaletra arm significantly (7.2 versus 9.6 days; P=0.02). Time to relief fever was almost similar across two groups (2.7 versus 3.1 days in ARB and Kaletra arms respectively). Peripheral oxygen saturation rate was different after seven days of admission across two groups significantly (94% versus 92% in ARB and Kaletra groups respectively) (P=0.02). Based on multiple linear regression analysis, IHD, Na level and oxygen saturation at the time of admission and type of therapy were the independent adjusted variables that determined the duration of hospitalization in patients with COVID-19.Conclusion: Our findings showed that Arbidol, compared to Kaletra, significantly contributes to clinical and laboratory improvements, including peripheral oxygen saturation, requiring ICU admissions, duration of hospitalization, chest CT involvements, WBC, and ESR. We suggest further studies on ARB using larger sample size and multicenter design.Trial registration: IRCT20180725040596N2 on 18 April 2020.

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“…In einer prospektiven Pilotstudie mit 63 Patienten mit schwerer COVID-19 war die Gabe von Tocilizumab mit einer gesteigerten Überlebenswahrscheinlichkeit assoziiert (Hazard Ratio 2,2, 95 %-KI 1,3–6,7, p < 0,05). IL-6-Spiegel erwiesen sich in dieser Studie jedoch nicht als Prädiktorwert für die Mortalität, wohl aber die D‑Dimere bei Studienbeginn [ 30 ]. Zum jetzigen Zeitpunkt ist noch keine Evidenz für die Wirksamkeit von Tocilizumab bei COVID-19-Patienten vorgelegt worden [ 31 , 32 ].…”

Section: Monokloanale Antikörper Zur Symptomatischen Behandlung Von Iunclassified

Monoklonale Antikörper zur antiinfektiven Therapie

Klug

Schnierle

Trebesch

2020

Bundesgesundheitsbl

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Zusammenfassung Ein Jahrhundert lang wurde die Serumtherapie von Seren tierischen Ursprungs und Hyperimmunglobulinen dominiert. Obwohl seit Ende der Achtzigerjahre des letzten Jahrhunderts zahlreiche monoklonale Antikörper (MAB) insbesondere zur Behandlung von immunologischen und onkologischen Erkrankungen entwickelt wurden, sollte es noch 20 Jahre bis zur Zulassung des ersten antiinfektiven MAB in der Europäischen Union dauern. In den folgenden 2 Dekaden kamen nur 2 weitere antiinfektive MAB hinzu. Interessanterweise werden zurzeit zur Bekämpfung der COVID-19-Pandemie zahlreiche MAB, die insbesondere in immunologischer Indikation zugelassen sind, zur Behandlung der Folgen der SARS-CoV-2-Infektion, wie Pneumonie oder Hyperimmunreaktion, eingesetzt. Im Folgenden werden die zugelassenen monoklonalen Antikörper zur Behandlung von Infektionskrankheiten vorgestellt. Darüber hinaus wird eine Übersicht über die aktuellen Entwicklungen, insbesondere bei der Therapie der SARS-CoV-2-Infektion, gegeben.

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Umifenovir susceptibility monitoring and characterization of influenza viruses isolated during ARBITR clinical study

Cited by 29 publications

References 31 publications

Antioxidant Potential of Antiviral Drug Umifenovir

Antioxidant Potential of Antiviral Drug Umifenovir

Effect of Arbidol on COVID-19: A Randomized Controlled Trial

Monoklonale Antikörper zur antiinfektiven Therapie

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