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Review
. 2020 May 13;158:104904.
doi: 10.1016/j.phrs.2020.104904. Online ahead of print.

The Possible Mechanisms of Action of 4-aminoquinolines (Chloroquine/Hydroxychloroquine) Against Sars-Cov-2 Infection (COVID-19): A Role for Iron Homeostasis?

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Free PMC article
Review

The Possible Mechanisms of Action of 4-aminoquinolines (Chloroquine/Hydroxychloroquine) Against Sars-Cov-2 Infection (COVID-19): A Role for Iron Homeostasis?

Eugenia Quiros Roldan et al. Pharmacol Res. .
Free PMC article

Abstract

The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course.

Keywords: COVID-19; Chloroquine/hydroxychloroquine; Inflammation; Iron; Sars-Cov-2; Thrombosis.

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E.Q.R. received travel grants from Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme and consultancy fees from Janssen-Cilag, ViiV Healthcare and Merck Sharp & Dohme. The remaining authors declare that they have no conflicts of interest.

Figures

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Fig. 1
Fig. 1
Graphic representation of the possible pharmacological effects (in green) of chloroquine and hydroxychloroquine as anti-viral, anti-inflammatory and anti-thrombotic drugs and their possible links with systemic and cellular iron homeostasis. For each pharmacological effect, hypothetical activities of the drugs on iron homeostasis are in blue, while the possible consequences on the virus and the host are in red.

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