Experimental and clinical evaluation of mefloquine effectiveness against the infection caused by SARS-CoV-2

About authors

Federal State Unitary Enterprise Research & Production Center "Pharmaceutical Protection" of Federal Medical Biological Agency, Khimki, Moscow Region, Russia

Correspondence should be addressed: Vadim D. Gladkikh
Vaschutinskoe shosse, 11, g. Himki, Moskovskaja oblast, 141402; ur.relbmar@7002hcikdalg

About paper

Author contribution: Filin KN — study concept and design, manuscript writing; Gladkikh VD — manuscript writing and editing; Bykov VN — literature analysis, data acquisition and processing, manuscript writing.

Compliance with ethical standards: animal experiments were approved by the Bioethics Commission of RMC “Home of Pharmacy» (protocol № 3.71/20 dated December 23, 2020); all the procedures involving animals were performed in accordance with the Directive N 2010/63/EC of the European Parliament and of the Council of the European Union "On the Protection of Animals Used for Scientific Purposes" of September 22, 2010. The animals' housing and care complied with GOST R 53434-2009 (Principles of Good Laboratory Practice) and the Guidelines for Laboratory Animals (2010). The clinical trial was approved by the Ethics Commitees of the clinical centers of Burnasyan Federal Medical Biophysical Center of FMBA, Federal Clinical Center for High Medical Technologies of FMBA, Center for Specialized Medical Assistance and Medical Technologies of FMBA, National Medical Research Center for Otorhinolaryngology of FMBA; the trial was carried out in accordance with the Russian Federation Government Decree № 441 of April 3, 2020; the informed consent was obtained from all patients.

Received: 2021-07-21 Accepted: 2021-08-26 Published online: 2021-09-30

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.

Keywords: COVID-19, SARS-CoV-2, antiviral activity, hydroxychloroquine, mefloquine