Elsevier

Nutrition Research

Volume 92, August 2021, Pages 109-128
Nutrition Research

Review Article
Potential molecular mechanisms of zinc- and copper-mediated antiviral activity on COVID-19

https://doi.org/10.1016/j.nutres.2021.05.008Get rights and content

Abstract

Novel coronavirus disease 2019 (COVID-19) has spread across the globe; and surprisingly, no potentially protective or therapeutic antiviral molecules are available to treat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, zinc (Zn) and copper (Cu) have been shown to exert protective effects due to their antioxidant, anti-inflammatory, and antiviral properties. Therefore, it is hypothesized that supplementation with Zn and Cu alone or as an adjuvant may be beneficial with promising efficacy and a favorable safety profile to mitigate symptoms, as well as halt progression of the severe form of SARS-CoV-2 infection. The objective of this review is to discuss the proposed underlying molecular mechanisms and their implications for combating SARS-CoV-2 infection in response to Zn and Cu administration. Several clinical trials have also included the use of Zn as an adjuvant therapy with dietary regimens/antiviral drugs against COVID-19 infection. Overall, this review summarizes that nutritional intervention with Zn and Cu may offer an alternative treatment strategy by eliciting their virucidal effects through several fundamental molecular cascades, such as, modulation of immune responses, redox signaling, autophagy, and obstruction of viral entry and genome replication during SARS-CoV-2 infection.

Keywords

Zinc (Zn)
Copper (Cu)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Coronavirus disease 2019 (COVID-19)
Gastrointestinal system
Trace elements

Abbreviations

ACE2
angiotensin-converting enzyme-2
ARDS
acute respiratory distress syndrome
ATOX1
human antioxidant protein 1
ATP7A
copper-ATPase
Bax
bcl-2-like protein 4
Bcl-2
B-cell lymphoma 2
CCS
copper chaperone for superoxide dismutase
CTR1
copper transporter protein
Cu
copper
IFN
interferons
IL
interleukin
MRE
metal-responsive element
MT
metallothionein
MTF-1
metal-responsive transcription factor-1
NAD
dependent deacetylase sirtuin-1
NF-κB
nuclear factor-κB
NK cells
natural killer cells
Nrf 2
nuclear erythroid factor 2
RdRP
RNA dependent RNA polymerase
ROS
reactive oxygen species
SARS-CoV-2
severe acute respiratory syndrome coronavirus-2
SIRT1
NAD-dependent deacetylase sirtuin-1
SOD
superoxide dismutase
Th
T helper cell
ZIP
Zrt-/Irt-like protein
Zn
zinc
ZnT
zinc transporter
Zo-1
zonula occludens-1

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1

The authors have contributed equally.

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