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Review
. 2020 May 6;101735.
doi: 10.1016/j.tmaid.2020.101735. Online ahead of print.

Therapeutic Use of Chloroquine and Hydroxychloroquine in COVID-19 and Other Viral Infections: A Narrative Review

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Free PMC article
Review

Therapeutic Use of Chloroquine and Hydroxychloroquine in COVID-19 and Other Viral Infections: A Narrative Review

Anwar M Hashem et al. Travel Med Infect Dis. .
Free PMC article

Abstract

The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rationalise the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.

Keywords: COVID-19; Chloroquine; Hydroxychloroquine; SARS-CoV-2.

Conflict of interest statement

Declaration of competing interest None declared.

Figures

Fig. 1
Fig. 1
Cellular and molecular possible sites of action of CQ ± HCQ as antiviral agents. (X) Represents the site of inhibition by CQ ± HCQ. (1) CQ and HCQ inhibit virus binding to its cell surface receptor, (2) CQ inhibits sialic acid biosynthesis through suppressing quinone reductase 2 activity which affect ACE2 receptor activity, (3) CQ and HCQ inhibit virus pH-dependent endocytosis through increasing pH, (4) CQ interferes with virus uncoating, (5) CQ interferes with assembly/budding leading to accumulation of viral vesicles within trans-Golgi network, (6) CQ interferes with lysosomal protein degradation and lysosomal fusion with autophagosomes. HCQ can interfere with lysosomal activity and prevent major histocompatibility complex (MHC) class II expression, (7) CQ interferes with TNF release and binding from macrophages and/to monocytes, (8) CQ inhibits phosphorylation of P38 MAPK and caspase in Th1 cells which in turn inhibits pro-inflammatory cytokines production and virus replication, (9) HCQ blocking of MCH expression prevents T cell activation, expression of CD145 and cytokines release, (10) HCQ impairs TLR signaling through increasing endosomal pH and interfering with TLR7 and TLR9 binding to their DNA/RNA ligands thereby inhibiting transcription of pro-inflammatory genes, (11) HCQ inhibits the binding of DNA to the cGAS and therefore reduce cytokines transcription and production. ACE2: Angiotensin converting enzyme 2; MHC: Major histocompatibility complex; TLR: Toll-like receptors; cGAS: Cyclic GMP-AMP synthase; MAPK: Mitogen-activated protein kinase. This figure was created with BioRender.com.

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