Chloroquine/hydroxychloroquine (CQ/HCQ)
Chloroquine, a 9-aminoquinolne, has been in clinical use since the 20th century. Hydroxychloroquine is the hydroxylated (and safer) form of chloroquine. CQ/HCQ was approved for the treatment of malaria and autoimmune disorders like rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, etc. Its antimalarial use has been largely suspended due to resistance (Devaux et al., 2020; Shama, 2020; D’Alessandro et al., 2020; Haladyj et al., 2018; Al-Bari, 2015; Savarino et al., 2003).
CQ/HCQ also has interesting antiviral activities and strong immunomodulatory effects that have led to robust scientific discussions that have culminated to several trials for possible approval for treatment of emerging viral diseases.
Its immunomodulatory effect occurs by the suppression of T-cells production/release of the cytokines - tumour necrosis alpha (TNF-α), the interleukins (IL 1, 2, 6 or 18) and interferon alpha and gamma (IFN-α,γ) which mediate the inflammatory complications of several viral diseases especially in COVID-19.
CQ/HCQ inhibits viral replication in many ways:
Inhibition of the pre-entry step of the viral cycle by interfering with viral particles binding to their cellular cell surface.
(b) Impairment of the early stage of virus replication by interfering with the pH-dependent endosome-mediated viral entry of susceptible viruses (like flaviviruses, retroviruses, and coronaviruses) by increasing both the endosomal and lysosomal pH leading to non-fusion with the host cell.
(c) Interference with the post-translational modification of the viral proteins thereby making the nascent viral particles non-infectious (Devaux et al., 2020; Shama, 2020; D’Alessandro et al., 2020; Haladyj et al., 2018; Al-Bari, 2015; Savarino et al., 2003).
Adverse effects are rarely seen with CQ/HCQ use. However, there could be gastrointestinal upset and hypersensitivity skin reactions (generalized pustular rash, urticaria, erythroderma). There are also chances of macular retinopathy, cardiomyopathy, arrhythmias, QT interval prolongation. There could also be dizziness, tinnitus, headaches and nightmares (D’Alessandro et al., 2020; Haladyj et al., 2018).