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).