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Review
. 2021 Dec;48(12):8195-8202.
doi: 10.1007/s11033-021-06770-7. Epub 2021 Oct 18.

Niclosamide for Covid-19: bridging the gap

Hayder M Al-Kuraishy  1 , Ali I Al-Gareeb  1 , Khalid J Alzahrani  2 , Athanasios Alexiou  3   4 , Gaber El-Saber Batiha  5
Affiliations
Review

Niclosamide for Covid-19: bridging the gap

Hayder M Al-Kuraishy et al. Mol Biol Rep. 2021 Dec.

Abstract

Aim/purpose: Niclosamide (NCL) is an anthelminthic drug, which is widely used to treat various diseases due to its pleiotropic anti-inflammatory and antiviral activities. NCL modulates of uncoupling oxidative phosphorylation and different signaling pathways in human biological processes. The wide-spectrum antiviral effect of NCL makes it a possible candidate for recent pandemic SARS-CoV-2 infection and may reduce Covid-19 severity. Therefore, the aim of the present study was to review and clarify the potential role of NCL in Covid-19.

Methods: This study reviewed and highlighted the protective role of NCL therapy in Covid-19. A related literature search in PubMed, Scopus, Web of Science, Google Scholar, and Science Direct was done.

Results: NCL has noteworthy anti-inflammatory and antiviral effects. The primary antiviral mechanism of NCL is through neutralization of endosomal PH and inhibition of viral protein maturation. NCL acts as a proton carrier, inhibits homeostasis of endosomal PH, which limiting of viral proliferation and release. The anti-inflammatory effects of NCL are mediated by suppression of inflammatory signaling pathways and release of pro-inflammatory cytokines. However, the major limitation in using NCL is low aqueous solubility, which reduces oral bioavailability and therapeutic serum concentration that reducing the in vivo effect of NCL against SARS-CoV-2.

Conclusions: NCL has anti-inflammatory and immune regulatory effects by modulating the release of pro-inflammatory cytokines, inhibition of NF-κB /NLRP3 inflammasome and mTOR signaling pathway. NCL has an anti-SARS-CoV-2 effect via interruption of viral life-cycle and/or induction of cytopathic effect. Prospective clinical studies and clinical trials are mandatory to confirm the potential role of NCL in patients with Covid-19 concerning the severity and clinical outcomes.

Keywords: Acute respiratory distress syndrome; Angiotensin-converting enzyme; Covid-19; Niclosamide; SARS-CoV-2 infection.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Inhibitory effects of niclosamide on SARS-CoV-2 infection and associated inflammatory pathways: SARS-CoV-2 through activation of macrophage, mammalian target of rapamycin (mTOR) and signal transducer and activator transcription 3 (STAT-3) leads to macrophage activation syndrome (MAS), cell apoptosis, and activation release of plasminogen activator inhibitor-1(PAI-1) respectively. As well, SARS-CoV-2 directly activates nuclear factor kappa B (NF-κB) and nod-like receptor pyrin 3 (NLRP3) inflammasome leading to release of pro-inflammatory cytokines with development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Niclosamide has inhibitory effects (formula image) on the SARS-CoV-2-mediated inflammatory signaling pathways and release of pro-inflammatory cytokines
Fig. 2
Fig. 2
Antiviral mechanisms of niclosamide: the antiviral mechanisms of niclosamide (NCL) are either of PH-dependent, which inhibit endosomal acidification, or PH-independent pathway. NCL inhibits mitochondrial oxidative phosphorylation with subsequent depletion of intracellular ATP, which trigger adenosine monophosphate protein kinase (AMPK) which directly blocks mTOR signaling pathway
See this image and copyright information in PMC

References

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