Figure 3. Possible mechanism of action of chloroquine and hydroxychloroquine in the intracellular space.

In COVID-19, CQ and HCQ impede the virus entry into the cells by interfering in ACE2 glycosylation and decreasing ACE2 affinity for the coronavirus S protein. Furthermore, CQ/HCQ is known to interfere with the TLR pathway involved in proinflammatory cytokine signaling. Inhibition of endosomal/lysosomal acidification by preventing pH reduction to prevent the release of the viral genome into the host cell cytoplasm is suggested to be another mechanism.

ACE2: Angiotensin-converting enzyme 2; cGAS: Cyclic GMP–AMP synthase; CQ: Chloroquine; HCQ: Hydroxychloroquine; S: Spike; STING: Stimulator of interferon genes; TLR: Toll-like receptor.