The aim of this work was to evaluate the effectiveness of quercetin addition to the treatment regimen for patients with COVID-19 associated pneumonia. Materials and methods. The effectiveness of two dosage forms of quercetin was studied in 200 patients, who were divided equally into the main and control groups. The main group patients received quercetin in addition to the basic therapy: intravenous drip of Quercetin/Polyvinylirolidone during the first 10 days followed by oral administration of Quercetin/Pectin over the next 10 days. Patients from the control group received only the basic therapy drugs. The study evaluated the dynamics of the disease symptoms (saturation level, respiratory rate, body temperature, cough, general weakness), as well as laboratory markers (C-reactive protein (CRP), ferritin, D-dimer). Results. Two dosage forms of quercetin consistently used in addition to the basic therapy improve pulmonary gas exchange and accelerate the lung function recovery. This is evidenced by a statistically significant majority of patients with positive dynamics in the symptoms of “Saturation level” and “Cough” as well as the meeting a complex indicator of the therapy effectiveness 2 days earlier than in the control group. The treatment regimen applied also helps to stabilize the level of D-dimer in the blood of the main group patients. Conclusions. The use of two dosage forms of quercetin in addition to the basic therapy accelerates the recovery of patients with coronavirus disease associated pneumonia and can help to prevent the progression of COVID-19 associated coagulopathy.
Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called Coronavirus Disease 2019 (COVID-19). Control of SARS-CoV-2 spread will depend on vaccine-induced or naturally acquired protective herd immunity. Until then, antiviral strategies are needed to manage COVID-19, but approved antiviral treatments, such as remdesivir, can only be delivered intravenously. Enisamium (laboratory code FAV00A, trade name Amizon®) is an orally active inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. Here we show that enisamium can inhibit SARS-CoV-2 infections in NHBE and Caco-2 cells. In vitro, the previously identified enisamium metabolite VR17-04 directly inhibits the activity of the SARS-CoV-2 RNA polymerase. Docking and molecular dynamics simulations suggest that VR17-04 prevents GTP and UTP incorporation. To confirm enisamium’s antiviral properties, we conducted a double-blind, randomized, placebo-controlled trial in adult, hospitalized COVID-19 patients, which needed medical care either with or without supplementary oxygen. Patients received either enisamium (500 mg per dose) or placebo for 7 days. A pre-planned interim analysis showed in the subgroup of patients needing supplementary oxygen (n = 77) in the enisamium group a mean recovery time of 11.1 days, compared to 13.9 days for the placebo group (log-rank test; p=0.0259). No significant difference was found for all patients (n = 373) or those only needing medical care (n = 296). These results thus suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis and that enisamium treatment shortens the time to recovery for COVID-19 patients needing oxygen.Significance statementSARS-CoV-2 is the causative agent of COVID-19. Although vaccines are now becoming available to prevent SARS-CoV-2 spread, the development of antivirals remains necessary for treating current COVID-19 patients and combating future coronavirus outbreaks. Here, we report that enisamium, which can be administered orally, can prevent SARS-CoV-2 replication and that its metabolite VR17-04 can inhibit the SARS-CoV-2 RNA polymerase in vitro. Moreover, we find that COVID-19 patients requiring supplementary oxygen, recover more quickly than patients treated with a placebo. Enisamium may therefore be an accessible treatment for COVID-19 patients.
Вірусні гепатити з гемоконтактним механізмом пе-редачі (гепатити В та С) і ВІЛ-інфекція залишаються однією з найбільш актуальних проблем охорони здоров'я у світі, особливо в країнах із низьким та середнім рівнем доходу. У світі зареєстровано приблизно 36,7 млн людей з ВІЛ-інфекцією, серед них -2,1 млн нових випадків захворювання у 2015 р. Найбільш уразливим регіоном залишається Африка на південь від Сахари -тут у 2015 р. проживало 25,6 млн людей з ВІЛ. На цей регіон припадає також майже дві третини загальної кількості нових випадків ВІЛ-інфекції у світі. Високими є показни-ки смертності від цього захворювання: більше 35 млн осіб загалом та приблизно 1,1 млн осіб у 2015 р. по-мерли від причин, пов'язаних з ВІЛ. За період з 2000 по 2015 рр. кількість нових випадків ВІЛ-інфекції зменши-лася на 35 %, а рівень смертності, пов'язаної зі СНІДом, знизився на 28 %, тобто було врятовано близько 8 млн людських життів у результаті міжнародних зусиль, спря-мованих на протидію ВІЛ/СНІДу [1].Згідно з експертними оцінками, на сьогодні лише 60 % людей з ВІЛ знають про свій статус, а решта 40 % (14 млн) людей потребують отримання доступу до послуг ВІЛ-тестування [1].У 2014 р. стратегія UNAIDS щодо прискорення за-ходів у відповідь на ВІЛ/СНІД запропонувала цільові показники прогресу у припиненні глобальної пандемії ВІЛ-інфекції після 2015 р.: 90-90-90 (до 2020 р.) та 95-95-90 (до 2030 р.). Це означає, якщо 90/95 % людей, що живуть з ВІЛ, будуть знати про свій ВІЛ-позитивний статус, і якщо 90/95 % людей, які знають про свій ВІЛ-позитивний статус, отримуватимуть антиретровірусну терапію (АРТ), то у 90/95 % людей, які отримують від-повідне лікування, рівень вірусного навантаження буде не визначатись, що суттєво зменшить ймовірність пе-редачі ВІЛ та подальше поширення збудника. Застосу-вання цього підходу дозволить запобігти до 2030 р. приблизно 28 млн нових випадків ВІЛ-інфекції, 21 млн смертей, обумовлених ВІЛ-інфекцією, уникнути додат-кових витрат у зв'язку з ВІЛ у розмірі 24 млрд доларів США та взагалі ліквідувати глобальну пандемію ВІЛ-інфекції [2].
Стисло висвітлено основні біографічні віхи й творчий доробок видатного вченого-інфекціоніста, доктора медичних наук, професора Олександри Семенівни Сокол, від дня народження якої виповнилося 100 років.
Background Enisamium (trade name Amizon MAX) is an orally available therapeutic that inhibits influenza A virus and SARS-CoV-2 replication and improves influenza patient recovery. We aimed to evaluate the clinical efficacy of enisamium treatment combined with standard care compared to standard care plus treatment with a placebo control in adult, hospitalized patients with moderate COVID-19 requiring external oxygen. This trial was registered with ClinicalTrials.gov under NCT04682873. Methods The study was a phase three, multi-center, double-blind, randomized, placebo-controlled trial conducted in 14 clinical centers. Hospitalized patients aged ≥18 years with laboratory-confirmed SARS-CoV-2 infection were eligible. Patients were randomly assigned to receive either enisamium (500 mg per dose, 4 times a day) or a placebo. The treatment lasted ≤7 days in case of early discharge from the hospital, or loss of the patient's ability to swallow due to the need for ventilation. All patients received standard of care as deemed necessary by the investigator and the health status of each patient. All patients received standard of care as deemed necessary by the investigator and each patient's health status. The primary outcome was an improvement of at least two points on an 8-point, modified WHO severity rating (SR) scale within 29 days of randomization. The primary and safety outcomes were analyzed in accordance to the intention-to-treat (ITT) principle. Findings A total of 592 patients were enrolled and randomized between May 2020 and March 2021. Only patients with a baseline SR of 4 (285 subjects or 48.1%) were included in the ITT analysis. Patients with a baseline SR of 5 were excluded as the interim analysis did not show relevant differences between the enisamium group and placebo in this sub-group. The patients with a baseline SR of 4 were divided into two groups: 142 (49.8%) were assigned to the enisamium group and 143 (50.2%) to the placebo group. No differences were observed between the safety or patient tolerability profiles of the enisamium and placebo treatment. Analysis of the ITT population showed that if patients were treated within 4 days of the onset of COVID-19 symptoms, the median time to improvement was 8 for the enisamium group and 13 days for the placebo group (p = 0.0051). For patients treated within 7 days of the onset of COVID-19 symptoms, the median time to improvement was 10 days for the enisamium group and 11 days for the placebo group (p = 0.0035). Comparison of groups using a stratified one-sided Logrank criterion (adjustment using stratification by age categories: "<40 years", "40-<65 years" and "≥65 years") showed statistically significant differences between the groups (p = 0.00945, one-sided). Interpretation Enisamium is safe to use in COVID-19 patients. In COVID-19 patients that did not require supplementary oxygen (SR = 5), standard treatment was sufficient to aid recovery and enisamium did not offer significant clinical benefits. However, we found that standard care combined with enisamium offers a significant clinical benefit when given to patients with moderate COVID-19 requiring supplementary oxygen (SR = 4), if enisamium is given within 7 days of the onset of symptoms. These data suggest that enisamium therapy can be used as therapy against SARS-CoV-2 infection in these patients. Funding Farmak JSC, Wellcome Trust, and Royal Society.
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