Experimental evaluation of the activity of the product meflochine against coronavirus SАRS-CoV-2

Filin KN1, Berzin IA2, Bykov VN1, Gladkikh VD1, Loginova SYa3, Savenko SV3, Schukina VN3
About authors

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

2 Federal Medical and Biological Agency, Moscow, Russia

3 Federal State Budgetary Institution "48 Central Research Institute" of the Ministry of Defense of the Russian Federation, Sergiev Posad-6, Russia

Received: 2020-06-25 Accepted: 2020-07-17 Published online: 2020-08-09
  1. Antibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013. B. Meyer, M.A. Müller, V.M. Corman, et al. Emerg. Infect. Dis. 2014; 20(4): 552-559.
  2. A novel coronavirus associated with severe acute respiratory yndrome. Ksiazek T.G., Erdman D, Goldsmith C.S., et al. N. Engl. J. Med. 2003; 348(20): 1947 - 1958.
  3. Novel coronavirus infections in Jordan, April 2012: Epidemiological findings from a retrospective investigation. B. Hijawi, et al. East Mediterr Health J. 2013; 19: 12-18.
  4. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. A.M. Zaki, et al. N. Engl. J. Med. 2012; 367: 1814-1820.
  5. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Desforges M, Le Coupanec A, Dubeau P, Bourgouin A, Lajoie L, Dubé M, Talbot PJ., et al. Viruses. 2019 Dec pii: E14. doi: 10.3390/v12010014.
  6. Chan KW, Wong VT2, Tang SCW1. COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease. Am J Chin Med. 2020; Mar 13: 1-26.
  7. Biot, C., Daher, W., Chavain, N., Fandeur, T., Khalife, J., Dive, D., & De Clercq, E. Design and Synthesis of Hydroxyferroquine Derivatives with Antimalarial and Antiviral Activities. Journal of Medicinal Chemistry. 2006; 49(9): 2845–2849.
  8. Biot, C., Daher, W., Chavain, N., Fandeur, T., Khalife, J., Dive, D., & De Clercq, E. Design and Synthesis of Hydroxyferroquine Derivatives with Antimalarial and Antiviral Activities. Journal of Medicinal Chemistry. 2006; 49(9): 2845–2849.
  9. De Wilde AH., Jochmans D., Posthuma CC. et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014 Aug;58(8): 4875-84. doi: 10.1128/AAC.03011-14.
  10. Liu J., Cao R., Xu M. et al.. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020; Mar 18: 6:16.
  11. Yao X., Ye F., Zhang M. et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020; Mar 9: pii: ciaa237.
  12. Sun W., He S., Martínez-Romero C. et al. Synergistic drug combination effectively blocks Ebola virus infection. Antiviral Research. 2017; Jan 137: 165-172.
  13. Balasubramanian, A., Teramoto, T., Kulkarni, A. A., Bhattacharjee, A. K., & Padmanabhan, R. Antiviral activities of selected antimalarials against dengue virus type 2 and Zika virus. Antiviral Research. 2017; 137: 141–150.
  14. McDonagh P., Sheehy PA., Norris JM. et al. Identification and characterisation of small molecule inhibitors of feline coronavirus replication. Vet Microbiol. 2014; Dec 5; 174(3-4): 438-447.
  15. McDonagh P., Sheehy PA., Fawcett A., Norris JM. Antiviral effect of mefloquine on feline calicivirus in vitro. Vet Microbiol. 2015; Apr 17; 176(3-4): 370-7.
  16. Fan HH., Wang LQ., Liu WL. et al. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model. Chin Med J (Engl). 2020 May 5; 133(9): 1051-1056.
  17. Guidelines for the experimental (preclinical) study of new pharmacological substances [Rukovodstvo po jeksperimental'nomu (doklinicheskomu) izucheniju novyh farmakologicheksih veshhestv]. M.: Minzdrav RF, 2005. (in Russian)
  18. Methodological approaches to the search for antiviral drugs, their testing and evaluation [Metodicheskie podhody k poisku antivirusnyh preparatov, ih ispytanie i ocenka]. N.A. Lagutkin, N.I. Mitin, V.A. Starovojtova i dr. v kn. Viral inhibitors and their mechanism of action [Virusnye ingibitory i mehanizm ih dejstvija] Pod red. V.P. Lozha, MK. Indulen, V.A. Kalnynja, N.A. Kanel' Riga, «Zinatne». 1977: 138-149. (in Russian)
  19. Chizhov N.P., Ershov F.I., Indulin MK. The basics of experimental chemotherapy for viral infections [Osnovy jeksperimental'noj himioterapii virusnyh infekcij]. Riga, 1988. (in Russian)
  20. Desjardins RE, Pamplin CL 3rd, von Bredow J. et al. Kinetics of a new antimalarial, mefloquine. Clin Pharmacol Ther. 1979 Sep; 26(3): 372-9.
  21. Karbwang, J., Na-Bangchang, K. Clinical application of mefloquine pharmacokinetics in the treatment ofP falciparummalaria. Fundamental & Clinical Pharmacology. 1994; 8(6): 491–502.
  22. Ferreira MVD, Vieira JLF, Almeida ED. et al. Pharmacokinetics of mefloquine administered with artesunate in patients with uncomplicated falciparum malaria from the Brazilian Amazon basin. Malar J. 2018 Jul 16; 17(1): 268.
  23. Rozman RS, Molek NA, Koby R. The absorption, distribution, and excretion in mice of the antimalarial mefloquine, erythro-2,8-bis(trifluoromethyl)-alpha-(2-piperidyl)-4-quinolinemethanol hydrochloride. Drug Metab Dispos. 1978 Nov-Dec; 6(6): 654-8.
  24. Tao Y., Xue J., Jiang B. [et al.]. Significance of higher drug concentration in erythrocytes of mice infected with Schistosoma japonicum and treated orally with mefloquine at single doses. Parasitol Res. 2015 Dec; 114(12): 4521-30.
  25. Pham YT, Nosten F, Farinotti R. et al. Cerebral uptake of mefloquine enantiomers in fatal cerebral malaria. Int J Clin Pharmacol Ther. 1999 Jan; 37(1): 58-61.