Chloroquine to fight COVID-19: A consideration of mechanisms and adverse
effects?
Abstract
The COVID-19 outbreak emerged in December 2019 and has rapidly become a
global pandemic. A great deal of effort has been made to find effective
drugs against this disease. Chloroquine (CQ) and hydroxychloroquine
(HCQ) have demonstrated great promise in treating COVID-19. CQ/HCQ have
been used to prevent and treat malaria and are efficacious
anti-inflammatory agents in rheumatoid arthritis and systemic lupus
erythematosus. These drugs have potential broad-spectrum antiviral
properties, and have been widely adopted for COVID-19 treatment and
clinical trials. In this review, we re-evaluated the treatment outcomes
and current hypothesis for the working mechanism of CQ/HCQ as COVID-19
therapy with a special focus on disruption of Ca2+ pathways. The
potential toxicity is also cautioned for its action on Ca2+ and
hyperpolarization-activated cyclic nucleotide-gated channels in cardiac
myocytes and neuronal cells. We propose that intracellular calcium
homeostasis is an alternative mechanism for CQ/HCQ pharmacology, which
should be considered when evaluating the risks and benefits of therapy
in these patients.