Zinc supplementation augments the suppressive effects of repurposed NF-κB inhibitors on ACE2 expression in human lung cell lines

Lee, Ming‐Cheng; Chen, Yin‐Kai; Tsai-Wu, Jyy-Jih; Hsu, Yih-Jen; Lin, Bor‐Ru

doi:10.1016/j.lfs.2021.119752

Cited by 18 publications

(12 citation statements)

References 32 publications

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“…IgM values in our patients have shown a negative correlation with serum zinc levels in females infected with SARS-CoV-2. Zinc augmented the suppressive effects of NF-κB on angiotensin-converting enzyme 2, a major receptor for SARS-CoV-2 infection [ 68 ], in a human lung cell line [ 69 ]. A study on hospitalized patients with COVID-19 in Iran has suggested that serum values of vitamin D, vitamin B12, and zinc at the time of admission negatively affect the clinical outcomes [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

The association between micronutrients and the SARS-CoV-2-specific antibodies in convalescent patients

et al. 2022

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Background Various micronutrients play key roles in the immune responses to viral infection, antibody synthesis, and susceptibility to infection. This study aimed to investigate the role of micronutrients on the immune responses following SARS-CoV-2 infection. Methods To evaluate humoral immunity following SARS-CoV-2 infection, the levels of SARS-CoV-2-specific IgM and IgG, as well as the concentrations of different micronutrients, were determined in 36 convalescent COVID-19 patients 60 days after infection. Furthermore, the correlation between biochemical and hematological parameters, clinical features, and the changes in adiposity with SARS-CoV-2 antibodies was evaluated. Results Serum IgM and IgG antibodies were detected in 38.8% and 83.3% of recovered patients after 60 days of COVID-19 infection, respectively. The values of SARS-CoV-2-specific IgG were negatively correlated with the number of the platelet. Moreover, the values of SARS-CoV-2-specific IgM were positively correlated with LDH and the vitamin B12 concentration. Furthermore, a gender-specific association of SARS-CoV-2-specific IgG and IgM with vitamins D as well as with B9 and zinc was observed. A significant negative correlation was observed between the values of IgG with vitamin D in male participants and a positive correlation was detected between IgG values and B9 in female participants. Moreover, IgM levels with serum zinc values in females were negatively correlated. Conclusion Our study suggests the potential role of micronutrients in gender-specific humoral immunity following SARS-CoV-2 infection. Further studies are required with a greater sample of subjects to substantiate the validity and robustness of our findings.

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Section: Discussionmentioning

confidence: 99%

The association between micronutrients and the SARS-CoV-2-specific antibodies in convalescent patients

et al. 2022

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“…Rnai I, et al indicated that nutritional intervention with Zn provided an adjutant therapy by eliciting their virucidal effects in the process of SARS-CoV-2 infection (80). Zn not only disrupted the balance of immune response, but also affected the expression of ACE2 receptors, which are required for SARS-CoV-2 entry into target cells (81). Moreover, Jennifer A Frontera, et al reported that Zn was associated with increased rates of recovery and reduced risk of mortality among COVID-19 patients (82).…”

Section: Discussionmentioning

confidence: 99%

Circulating trace elements status in COVID-19 disease: A meta-analysis

Luo²,

Liang³

2022

Front. Nutr.

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Trace elements are a group of essential metals or metalloids, which are necessary for life, and present in minute amounts. Despite substantial researches highlighting the importance of trace elements in Coronavirus disease 2019 (COVID-19) diseases, a thorough evaluation of the levels of circulating trace elements is lacking. Therefore, we conducted a systematic review and meta-analysis to evaluate the trace element status (Zn, Fe, Cu, Mg, and Se) in COVID-19 disease. We also assessed the relationship between circulating trace elements and COVID-19 disease severity and survival status during follow-up. We searched comprehensively MEDLINE, Web of Science, CNKI, and WangFang databases without language restriction, between November 1, 2019 and April 1, 2022. The search identified 1,566 preliminary references. A total of 49 studies met the eligibility criteria and were included in the review, and 42 studies were included in the final meta-analysis. Meta-analysis showed that COVID-19 patients had significantly lower circulating Zn (SMD: −0.83, 95% CI: −1.19 to −0.46, P < 0.001), Fe (SMD: −1.56, 95% CI: −2.90 to −0.21, P = 0.023), and Se (SMD: −0.75, 95% CI: −0.94 to −0.56, P < 0.001) levels than healthy controls, and circulating Zn (SMD: −0.47, 95% CI: −0.75 to −0.18, P = 0.002), Fe (SMD: −0.45, 95% CI: −0.79 to −0.12, P = 0.008), and Se (SMD: −0.27, 95% CI: −0.49 to −0.04, P = 0.020) levels were associated with the presence of severity status in COVID-19 patients. Moreover, circulating Fe levels in non-survivors were significantly lower than survivors in COVID-19 (SMD: −0.28, 95% CI: −0.44 to −0.12, P = 0.001). However, there was no significant difference in Cu and Mg levels between COVID-19 patients and controls, severity and non-severity status, and survivors and non-survivors (all P > 0.05). Taken together, COVID-19 patients displayed lower circulating levels of Zn, Fe, and Se, and their levels were associated with severity status. Moreover, circulating Fe levels may provide part of the explanation for the unfavorable survival status. Therefore, we presumed optimistically that supplements of trace elements might provide an adjutant treatment in the early stages of COVID-19.Systematic review registration[https://www.crd.york.ac.uk/prospero], identifier [CRD42022348599].

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“…The results showed that emetine alone could clearly reduce ACE2 mRNA and protein levels, but in the presence of zinc sulfate supplementation, emetine had more suppressive effects on ACE2 expression in H322M and Calu-3 cells. 59 …”

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

Different Aspects of Emetine’s Capabilities as a Highly Potent SARS-CoV-2 Inhibitor against COVID-19

Valipour

2022

ACS Pharmacol. Transl. Sci.

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In the global movement to find the appropriate agents to fight the coronavirus disease of 2019 (COVID-19), emetine is one of the strongest anti-SARS-CoV-2 compounds with sub-micromolar EC 50 values, identified in several studies and high-throughput screening efforts. The reported anti-SARS-CoV-2 mechanisms indicate the effect of this compound on both virus-based and host-based targets. In addition to having excellent antiviral effects, emetine can relieve COVID-19 patients by reducing inflammation through inhibitory activity against NF-κB by the mechanism of IκBα phosphorylation inhibition; it can also limit the lipopolysaccharide-induced expression of pro-inflammatory cytokines TNFα, IL-1β, and IL-6. Emetine also can well reduce pulmonary arterial hypertension as an important COVID-19 complication by modulating a variety of cellular processes such as the Rho-kinase/CyPA/Bsg signaling pathway. The therapeutic value of emetine for combating COVID-19 was highlighted when in vivo pharmacokinetic studies showed that the concentration of this compound in the lungs increases significantly higher than the EC 50 of the drug. Despite its valuable therapeutic effects, emetine has some cardiotoxic effects that limit its use in high doses. However, high therapeutic capabilities make emetine a valuable lead compound that can be used for the design and development of less toxic anti-COVID-19 agents in the future. This Review provides a collection of information on the capabilities of emetine and its potential for the treatment of COVID-19, along with structural analysis which could be used for further research in the future.

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Zinc supplementation augments the suppressive effects of repurposed NF-κB inhibitors on ACE2 expression in human lung cell lines

Cited by 18 publications

References 32 publications

The association between micronutrients and the SARS-CoV-2-specific antibodies in convalescent patients

The association between micronutrients and the SARS-CoV-2-specific antibodies in convalescent patients

Circulating trace elements status in COVID-19 disease: A meta-analysis

Different Aspects of Emetine’s Capabilities as a Highly Potent SARS-CoV-2 Inhibitor against COVID-19

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