Chloroquine against Covid-19?

The antimalarial drug, chloroquine has been claimed effective in the treatment of patients infected by the novel emerged coronavirus, Covid-19 by Chienese experts [1]. Touret and de Lamballerie [2] reviewed the knowledge on antiviral effect of this drug. The growth of many different viruses can be inhibited in cell culture by both chloroquine and hydroxychloroquine, including the SARS coronavirus, but there was pure in vitro–in vivo correlation in case of influenza and dengue virus infections. Similarly, chloroquine was active ex vivo but not in vivo in the case of ebola virus in mice and influenza virus in ferrets. Controversial results were obtained with chikungunya virus (CHIKV), as well. So, based on the assessment of previous trials the authors conclude that, to date, no acute virus infection has been successfully treated by chloroquine in humans [2]. They daubt the efficacy against Covid-19, as no data has been provided yet to support the efficacy. They urge Chinese scientists to report the interim results of the several clinical trials currently running in China as soon as they are available.

Chloroquine is a racemic drug; its enantioseparation has been studied by several groups using cyclodextrins as chiral selectors. One of the systematic investigations showed that the presence of carboxyl or sulfate functional groups on CD derivatives is advantageous for the resolution of chloroquine enantiomers [3].

Although chloroquine is a hydrophilic drug, a recent study showed that both solubility and bioavailability of chloroquine diphosphate could be enhanced and some of its side effects reduced after encapsulation with cyclodextrins [4]. The 1:1 stoichiometry of the complexes and preference of the βCD cavity were proved.

[1] Gao, J., Tian, Z., Yang, X. (2020) Breakthrough: chloroquine phosphate has shown ap-parent efficacy in treatment of COVID-19 associated pneumonia in clinical studies.Biosci. Trends.https://doi.org/10.5582/bst.2020.01047.

[2] Touret, F., de Lamballerie, X. (2020) Commentary of Chloroquine and COVID-19. Antiviral Research 177,  104762. https://doi.org/10.1016/j.antiviral.2020.104762

Nemeth, K., Tarkanyi, G., Varga, E., Imre, T., Mizsei, R.., Ivanyi, R., Visy, J., Szeman, J., Jicsinszky, L., Szente, L., Simonyi, M. (2011) Enantiomeric separation of antimalarial drugs by capillary electrophoresis using neutral and negatively charged cyclodextrins. Journal of Pharmaceutical and Biomedical Analysis, 54(3), 475-481. https://doi.org/10.1016/j.jpba.2010.09.020

Roy, A., Saha, S., Roy, D., Bhattacharyya, S., Roy, M.N. (2020) Formation & specification of host–guest inclusion complexes of an anti-malarial drug inside into cyclic oligosaccharides for enhancing bioavailability. Journal of Inclusion Phenomena and Macrocyclic Chemistry, in press