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OpenSourceMalaria / pipeline_living_review

An open, living review of the current antimalarial pipeline
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MoA of Hydroxychloroquine (HQC) #5

Open edwintse opened 4 years ago

edwintse commented 4 years ago

As you may know, chloroquine (CQ) has been used as an antimalarial since the 1940s. Resistance began to develop about a decade later but it is still used today as it's on the WHO Model List of Essential Medicines.

CQ, and it's structurally related quinoline drugs (quinine/mepacrine/mefloquine/HCQ), act through the disruption of haemoglobin digestion (haem to haemozoin conversion) in the blood stage of the malaria parasite.[1,2] It has also been shown that CQ and HCQ are able to diffuse through the cell membrane, become protonated, and raise the endosomal pH levels.[3]

With respect to the current COVID-19, it is the latter of these mechanisms lead to the prevention of virus particles (like SARS-CoV and SARS-CoV-2) from fusing to the membrane and entering the cell. In addition to this, it has been shown that CQ and HCQ are able to inhibit glycosylation of the ACE2 receptor which allows the relevant coronaviruses to enter the cell.[4] These, in relation to COVID-19, have been supported by a number of recent publications.[5,6,7,8,9]

References

1 M. Foley et al. Int. J. Parasitol. 1997, 27, 231-240. doi: 10.1016/S0020-7519(96)00152-X 2 J. M. Combrinck et al. ACS Chem. Biol. 2013, 8, 133-137. doi: 10.1021/cb300454t 3 J. Ducharme et al. Clin. Pharmacokinet. 1996, 31, 257-274. doi: 10.2165/00003088-199631040-00003 4 M. J. Vincent et al. Virol. J. 2005, 2, No. 69. doi: 10.1186/1743-422X-2-69 5 M. Wang et al. Cell Res. 2020, 30, 269-271. doi: 10.1038/s41422-020-0282-0 6 J. Liu et al. Cell Discov. 2020, 6, No. 16. doi: 10.1038/s41421-020-0156-0 7 J. Fantinin et al. Int. J. Antimicrob. Agents 2020, In Press. doi: 10.1016/j.ijantimicag.2020.105960 8 A. K. Singh et al. Diabetes Metab. Syndr. 2020, 14, 241-246. doi: 10.1016/j.dsx.2020.03.011 9 K. M. Kapoor et al. 2020, medRxiv preprint Literature Review. doi: 10.1101/2020.03.24.20042366

drc007 commented 4 years ago

@edwintse The structures are incorrect, should be quinoline not isoquinoline

edwintse commented 4 years ago

Oops, thanks @drc007. Now fixed