The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis?

Quiros-Roldan, Eugenia; Biasiotto, Giorgio; Magro, Paola

doi:10.1016/j.phrs.2020.104904

Cited by 108 publications

(116 citation statements)

References 139 publications

(191 reference statements)

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“…High iron storage in these cells will help viral replication [31]. CQ and HCQ may inhibit the release of IL-6, IL-1B, and TNF-ɑ and so cause a decrease in hepcidin and inhibit viral replication [32]. Also, some drugs like tocilizumab suppress the synthesis of hepcidin [33].…”

Section: Iron (Ferrous)mentioning

confidence: 99%

A Review on the Serum Electrolytes and Trace Elements Role in the Pathophysiology of COVID-19

Taheri

Bahrami

Habibi

et al. 2020

Biol Trace Elem Res

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All the world is involved in the COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus is a positive-sense RNA and has an envelope. There is no specific drug for this disease and treatment methods are limited. Malnutrition and electrolyte imbalance can make dysfunction in the immune system and impairment of the immune system causes increasing the risk of infection. Understanding the aspects of biological features of the virus will help the development of diagnostic tests, pharmacological therapies, and vaccines. Here, we review and discuss increasing and decreasing some trace elements and imbalance of serum and plasma electrolytes involving in COVID-19.

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Section: Iron (Ferrous)mentioning

confidence: 99%

A Review on the Serum Electrolytes and Trace Elements Role in the Pathophysiology of COVID-19

Taheri

Bahrami

Habibi

et al. 2020

Biol Trace Elem Res

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show abstract

“…HCQ has recently been the subject of renewed interest both as a therapy for the disease caused by SARS-CoV-2 [51][52][53], and prophylaxis [54]. Interestingly, HCQ can intervene as a competitor for absorption by binding to the cellular receptor [55], or onto iron homeostasis [56].…”

Section: Introductionmentioning

confidence: 99%

New Anti SARS-Cov-2 Targets for Quinoline Derivatives Chloroquine and Hydroxychloroquine

Gentile

Fuochi

Rescifina

et al. 2020

IJMS

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The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a severe global health crisis. In this paper, we used docking and simulation methods to identify potential targets and the mechanism of action of chloroquine (CQ) and hydroxychloroquine (HCQ) against SARS-CoV-2. Our results showed that both CQ and HCQ influenced the functionality of the envelope (E) protein, necessary in the maturation processes of the virus, due to interactions that modify the flexibility of the protein structure. Furthermore, CQ and HCQ also influenced the proofreading and capping of viral RNA in SARS-CoV-2, performed by nsp10/nsp14 and nsp10/nsp16. In particular, HCQ demonstrated a better energy binding with the examined targets compared to CQ, probably due to the hydrogen bonding of the hydroxyl group of HCQ with polar amino acid residues.

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“…Interference with iron accumulation has been postulated as one of the mechanisms by which chloroquine and hydroxychloroquine are beneficial against COVID-19 [62]. This could occur via an inhibitory effect of antimalarials on iron uptake into tissues (Fig.…”

Section: Effect Of Antimalarials On Iron Metabolismmentioning

confidence: 99%

Effects of Antimalarial Drugs on Neuroinflammation-Potential Use for Treatment of COVID-19-Related Neurologic Complications

Ong

Wang

et al. 2020

Mol Neurobiol

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The SARS-CoV-2 virus that is the cause of coronavirus disease 2019 (COVID-19) affects not only peripheral organs such as the lungs and blood vessels, but also the central nervous system (CNS)—as seen by effects on smell, taste, seizures, stroke, neoropathological findings and possibly, loss of control of respiration resulting in silent hypoxemia. COVID-19 induces an inflammatory response and, in severe cases, a cytokine storm that can damage the CNS. Antimalarials have unique properties that distinguish them from other anti-inflammatory drugs. (A) They are very lipophilic, which enhances their ability to cross the blood-brain barrier (BBB). Hence, they have the potential to act not only in the periphery but also in the CNS, and could be a useful addition to our limited armamentarium against the SARS-CoV-2 virus. (B) They are non-selective inhibitors of phospholipase A2 isoforms, including cytosolic phospholipase A2 (cPLA2). The latter is not only activated by cytokines but itself generates arachidonic acid, which is metabolized by cyclooxygenase (COX) to pro-inflammatory eicosanoids. Free radicals are produced in this process, which can lead to oxidative damage to the CNS. There are at least 4 ways that antimalarials could be useful in combating COVID-19. (1) They inhibit PLA2. (2) They are basic molecules capable of affecting the pH of lysosomes and inhibiting the activity of lysosomal enzymes. (3) They may affect the expression and Fe2+/H+ symporter activity of iron transporters such as divalent metal transporter 1 (DMT1), hence reducing iron accumulation in tissues and iron-catalysed free radical formation. (4) They would affect viral replication. The latter may be related to their effect on inhibition of PLA2 isoforms. Inhibition of cPLA2 impairs an early step of coronavirus replication in cell culture. In addition, a secretory PLA2 (sPLA2) isoform, PLA2G2D, has been shown to be essential for the lethality of SARS-CoV in mice. It is important to take note of what ongoing clinical trials on chloroquine and hydroxychloroquine can eventually tell us about the use of antimalarials and other anti-inflammatory agents, not only for the treatment of COVID-19, but also for neurovascular disorders such as stroke and vascular dementia.

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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?

Cited by 108 publications

References 139 publications

A Review on the Serum Electrolytes and Trace Elements Role in the Pathophysiology of COVID-19

A Review on the Serum Electrolytes and Trace Elements Role in the Pathophysiology of COVID-19

New Anti SARS-Cov-2 Targets for Quinoline Derivatives Chloroquine and Hydroxychloroquine

Effects of Antimalarial Drugs on Neuroinflammation-Potential Use for Treatment of COVID-19-Related Neurologic Complications

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