Chloroquine is a 4-aminoquinoline compound long used as an antimalarial and antirheumatic agent, acting principally as a weak base that accumulates within acidic intracellular compartments and raises endosomal and lysosomal pH. In the malaria parasite this interferes with heme detoxification in the digestive vacuole…
Chloroquine is a 4-aminoquinoline compound long used as an antimalarial and antirheumatic agent, acting principally as a weak base that accumulates within acidic intracellular compartments and raises endosomal and lysosomal pH. In the malaria parasite this interferes with heme detoxification in the digestive vacuole; in other contexts the same alkalinizing effect impairs endosomal acidification, antigen processing, and autophagy. These properties prompted investigation of chloroquine and its hydroxylated analogue, hydroxychloroquine, as candidate antivirals during the COVID-19 pandemic, on the hypothesis that raised endosomal pH might hinder viral entry and post-entry processing of SARS-CoV-2. Clinical evaluation examined viral kinetics in mild disease treated with chloroquine-containing regimens versus standard of care, and assessed effects on clinical improvement and mortality in hospitalized patients. The drug class carries a defined toxicity profile, notably QT-interval prolongation, retinal injury with prolonged exposure, and gastrointestinal effects, which constrain dosing and demand monitoring. Pharmacologically, chloroquine illustrates how a single mechanism, lysosomotropic accumulation, can underlie activity against unrelated targets spanning protozoal infection, autoimmune inflammation, and viral replication. Research in this area weighs in vitro plausibility against controlled clinical evidence, the central question being whether laboratory activity translates into measurable patient benefit.
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