An article to sort out the mechanism of action of hydroxychloroquine (HCQ) and chloroquine (CQ)

Hydroxychloroquine (HCQ), originally used as an antimalarial drug, and, to a lesser extent, chloroquine (CQ), are now being used to treat a variety of diseas.

To date, CQ and HCQ have been reported to inhibit four groups of cellular functions : (i) endolysosomal activity, including autophagy; (ii) cytokine signaling, including endosomal Toll-like receptors (TLRs); (iii) NADPH oxidase (NOX) signaling; (iv) Calcium (Ca 2+ ) mobilization from the endoplasmic reticulum (E.

Effects of HCQ on the immune system:

HCQ is administered orally in tablet form as hydroxychloroquine sulfa.

Open Issues:

(i) Investigate whether all of the HCQ modes of action described in the in vitro experiments are patient-relevant and whether one of these mechanisms is primarily responsible for the observed side effec.

(ii) Determining whether HCQ has other molecular effects than those described above, which can help to better understand patient outcomes from HCQ treatme.

(iii) Chemical modification of HCQ to make it more effective and less toxic, thereby making it more suitable for the treatment of other diseases (eg certain cancer.

(iv) To understand how the anti-inflammatory effects of HCQ affect the antiviral and antitumor effects of the drug in patients, and whether this may explain the observed differences between in vitro and in vivo resul.

In conclusion, while it is tempting to search for the unifying mechanism of action of HCQ, current knowledge suggests that this small molecule has more than one targ.