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The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis?
Pharmacol Res. 2020 08; 158:104904.PR

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.

Authors+Show Affiliations

University Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy.Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Clinical Chemistry Laboratory, Cytogenetics and Molecular Genetics Section, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.University Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy.Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Clinical Chemistry Laboratory, Cytogenetics and Molecular Genetics Section, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy. Electronic address: isabella.zanella@unibs.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

32430286

Citation

Quiros Roldan, Eugenia, et al. "The Possible Mechanisms of Action of 4-aminoquinolines (chloroquine/hydroxychloroquine) Against Sars-Cov-2 Infection (COVID-19): a Role for Iron Homeostasis?" Pharmacological Research, vol. 158, 2020, p. 104904.
Quiros Roldan E, Biasiotto G, Magro P, et al. The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? Pharmacol Res. 2020;158:104904.
Quiros Roldan, E., Biasiotto, G., Magro, P., & Zanella, I. (2020). The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? Pharmacological Research, 158, 104904. https://doi.org/10.1016/j.phrs.2020.104904
Quiros Roldan E, et al. The Possible Mechanisms of Action of 4-aminoquinolines (chloroquine/hydroxychloroquine) Against Sars-Cov-2 Infection (COVID-19): a Role for Iron Homeostasis. Pharmacol Res. 2020;158:104904. PubMed PMID: 32430286.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? AU - Quiros Roldan,Eugenia, AU - Biasiotto,Giorgio, AU - Magro,Paola, AU - Zanella,Isabella, Y1 - 2020/05/13/ PY - 2020/04/20/received PY - 2020/05/04/revised PY - 2020/05/06/accepted PY - 2020/5/21/pubmed PY - 2020/7/21/medline PY - 2020/5/21/entrez KW - COVID-19 KW - Chloroquine/hydroxychloroquine KW - Inflammation KW - Iron KW - Sars-Cov-2 KW - Thrombosis SP - 104904 EP - 104904 JF - Pharmacological research JO - Pharmacol Res VL - 158 N2 - 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. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/32430286/The_possible_mechanisms_of_action_of_4_aminoquinolines__chloroquine/hydroxychloroquine__against_Sars_Cov_2_infection__COVID_19_:_A_role_for_iron_homeostasis L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(20)31212-3 DB - PRIME DP - Unbound Medicine ER -