The host targeting effect of chloroquine in malaria

Highlights

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  Chloroquine/hydroxychloroquine is an old anti-malarial drug belongs to 4-aminoquinolines.

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  Chloroquine has additional anti-virus, anti-bacteria, anti-protozoan, anti-autoimmunity and anti-cancer effects.

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  Mechanism of action of chloroquine in malaria and other diseases is not understood well.

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  Chloroquine directly targets Plasmodium hemoglobin degradation pathway.

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  In addition, chloroquine may directly target host’s autophagy, innate and adaptive immunity in malaria.

Abstract

Due to the rapid onset and spread of the COVID-19 pandemic, the treatment of COVID-19 patients by hydroxychloroquine alone or in combination with other drugs has captured a great deal of attention and triggered considerable debate. Historically, the worldwide use of quinoline based-drugs has led to a spectacular reduction in death from malaria. Unfortunately, scientists have been forced to seek alternative drugs to treat malaria due to the emergence of chloroquine-resistant parasites in the 1960s. The repurposing of hydroxychloroquine against viral infections, various types of cancer and autoimmune diseases has been ongoing for more than 70 years, with no clear understanding of its mechanism of action (MOA). Here, we closely examine the MOA of this old but influential drug in and beyond malaria. Better insights into how chloroquine targets the host’s cellular and immune responses may help to develop applications against to new pathogens and diseases, and perhaps even restore the clinical utility of chloroquine against malaria.