When evaluating the effectiveness of the drug Mefloquine against SARS-Cov-2 coronavirus, in vitro experiments examined its toxicity for African green monkey kidney cell culture - Vero C1008, as well as antiviral activity against SARS-Cov-2, which was evaluated by suppressing the cytopathic effect the virus. A study of the toxicity of the drug Mefloquine showed that the concentration at which the drug exerts a cytopathic effect against 50% of Vero C1008 cells is 4.5 μg / ml. The maximum tolerated concentration (MTD) of Mefloquine is 2.25 μg / ml. A study of the effectiveness showed that 1 day after infection, the antiviral effect of Mefloquine was recorded when the drug was added 24 hours and 1 hour before infection with SARS-CoV-2, as well as when it was added 1 hour after infection, the cell culture was already at a concentration of 0.5 μg / ml Mefloquine at a concentration of 2 μg / ml, added to the Vero C1008 cell culture 1 hour after the introduction of SARS-CoV-2, completely blocked the action of the virus for 2 days after infection.
The aim of the study was to clarify the toxicity of mefloquine and to evaluate the effectiveness of its use for Syrian hamsters infected with sARS-Cov-2.Material and methods. The experiments were performed on 96 Syrian hamsters. The toxicity of mefloquine was determined with a single administration, as well as with a course of administration at doses comparable to therapeutic for humans. To study the effectiveness of the drug against SARS-CoV-2 infection, a comprehensive indicator of the state of lung tissue and a comparison of the dynamics of viral load in the lungs were used.Results. The LD50 of mefloquine with a single oral administration is 817 mg/kg, the maximum tolerated dose is 600 mg/kg. When administered for 7 days at a cumulative dose of 900 mg/kg, no death was observed. Administration of mefloquine to animals infected with SARS-CoV-2 was accompanied by a decrease in the severity of lung damage and a faster decrease of viral load in the lung tissue.
The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 ± 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 ± 0.21 lg PFU/g) and ribavirin group (5.2 ± 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (р < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (р < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (р > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.
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