The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis?
COVID-19
Chloroquine/hydroxychloroquine
Inflammation
Iron
Sars-Cov-2
Thrombosis
Journal
Pharmacological research
ISSN: 1096-1186
Titre abrégé: Pharmacol Res
Pays: Netherlands
ID NLM: 8907422
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
20
04
2020
revised:
04
05
2020
accepted:
06
05
2020
pubmed:
21
5
2020
medline:
21
7
2020
entrez:
21
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32430286
pii: S1043-6618(20)31212-3
doi: 10.1016/j.phrs.2020.104904
pmc: PMC7217799
pii:
doi:
Substances chimiques
Antiviral Agents
0
Hydroxychloroquine
4QWG6N8QKH
Chloroquine
886U3H6UFF
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
104904Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
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.
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