Why the lower reported prevalence of asthma in patients diagnosed with COVID-19 validates repurposing EDTA solutions to prevent and manage treat COVID-19 disease

Cashman, Daniel P.

doi:10.1016/j.mehy.2020.110027

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…A possible mechanism that could partly explain this increased risk involves a calcium-sensitive interaction of SARS-CoV-2 with the ACE-2 receptor (its entry point in human cells). Hence, more available calcium could ease the entry of SARS-CoV-2 in the host cells [ 46 ]. However, this result remains unclear and warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort

Deschasaux

Srour

Bourhis

et al. 2021

BMC Med

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Background Nutritional factors are essential for the functioning of the immune system and could therefore play a role in COVID-19 but evidence is needed. Our objective was to study the associations between diet and the risk of SARS-CoV-2 infection in a large population-based sample. Methods Our analyses were conducted in the French prospective NutriNet-Santé cohort study (2009–2020). Seroprevalence of anti-SARS-CoV-2 antibodies was assessed by ELISA on dried blood spots. Dietary intakes were derived from repeated 24 h dietary records (at least 6) in the two years preceding the start of the COVID-19 pandemic in France (February 2020). Multi-adjusted logistic regression models were computed. Results A total of 7766 adults (70.3% women, mean age: 60.3 years) were included, among which 311 were positive for anti-SARS-CoV-2 antibodies. Dietary intakes of vitamin C (OR for 1 SD=0.86 (0.75–0.98), P=0.02), vitamin B9 (OR=0.84 (0.72–0.98), P=0.02), vitamin K (OR=0.86 (0.74–0.99), P=0.04), fibers (OR=0.84 (0.72–0.98), P=0.02), and fruit and vegetables (OR=0.85 (0.74–0.97), P=0.02) were associated to a decreased probability of SARS-CoV-2 infection while dietary intakes of calcium (OR=1.16 (1.01–1.35), P=0.04) and dairy products (OR=1.19 (1.06–1.33), P=0.002) associated to increased odds. No association was detected with other food groups or nutrients or with the overall diet quality. Conclusions Higher dietary intakes of fruit and vegetables and, consistently, of vitamin C, folate, vitamin K and fibers were associated with a lower susceptibility to SARS-CoV-2 infection. Beyond its established role in the prevention of non-communicable diseases, diet could therefore also contribute to prevent some infectious diseases such as COVID-19.

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Section: Discussionmentioning

confidence: 99%

Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort

Deschasaux

Srour

Bourhis

et al. 2021

BMC Med

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“…Further experiments revealed that pharmacological manipulations, which reduced the rise in [Ca 2+ ] in , were able to inhibit distinct steps of PDCoV replication. In the context of these findings, it is tempting to speculate that the effects of Ca 2+ -channel blockers [48,49] and Ca 2+ chelators [50] on reducing mortality from Covid-19 could be directly or indirectly related to the function of the E-protein in elevating [Ca 2+ ] in .…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 envelope-protein corruption of homeostatic signaling mechanisms in mammalian cells

Schulze

Hartel

Hoeler

et al. 2021

Preprint

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During a SARS-CoV2 infection, host cells produce large amounts of the viral envelope protein (Ep-CoV2). Ep-CoV2 is partially inserted into the membrane of nascent viral particles and into cellular membranes. To mimic the pathophysiological impact of the cellular protein fraction, Ep-CoV2 was overexpressed in mammalian cells and effects on key signaling parameters were monitored. By tagging with green fluorescent protein (GFP), we found that Ep-CoV2 protein is mostly present in the endoplasmic reticulum with additional trace amounts in the plasma membrane. We observed that wild-type Ep-CoV2 and, to a lesser extent, its mutants (N15A, V25F) corrupted some of the most important homeostatic mechanisms in cells. The same was observed with isolated transmembrane domains of the protein. The Ep-CoV2-evoked elevation of intracellular Ca2+ and pH as well as the induced membrane depolarization produced by the presence of the protein interfere with major signal transduction cascades in host cells. These functions of Ep-CoV2, which likely contribute to the pathogenesis of the viral protein, result from the ion-channel activity of the viral protein. Two independent assays, a functional reconstitution of Ep-CoV2 protein in artificial membranes and a rescue of K+-deficient yeast mutants, confirm that Ep-CoV2 generates a cation-conducting channel with a low unitary conductance and a complex ion selectivity. The data presented here suggest that specific channel function inhibitors of Ep-CoV2 can provide cell protection and virostatic effects.

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“… 26 More evidence that interference with the cellular Ca 2+ balance suppresses viral growth comes from nebulizers used for asthma medications. Nebulizers are supplemented with EDTA as a preservative, which may help to deplete extracellular Ca 2+ 27 and may provide a clue as to why asthma (despite being a respiratory illness) is not on the top ten list of chronic health problems of people who died of COVID-19.…”

mentioning

confidence: 99%

Inhibitors of L-Type Calcium Channels Show Therapeutic Potential for Treating SARS-CoV-2 Infections by Preventing Virus Entry and Spread

et al. 2021

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COVID-19 is caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2). The virus is responsible for an ongoing pandemic and concomitant public health crisis around the world. While vaccine development is proving to be highly successful, parallel drug development approaches are also critical in the response to SARS-CoV-2 and other emerging viruses. Coronaviruses require Ca 2+ ions for host cell entry, and we have previously shown that Ca 2+ modulates the interaction of the viral fusion peptide with host cell membranes. In an attempt to accelerate drug repurposing, we tested a panel of L-type calcium channel blocker (CCB) drugs currently developed for other conditions to determine whether they would inhibit SARS-CoV-2 infection in cell culture. All the CCBs tested showed varying degrees of inhibition, with felodipine and nifedipine strongly limiting SARS-CoV-2 entry and infection in epithelial lung cells at concentrations where cell toxicity was minimal. Further studies with pseudotyped particles displaying the SARS-CoV-2 spike protein suggested that inhibition occurs at the level of virus entry. Overall, our data suggest that certain CCBs have the potential to treat SARS-CoV-2 infections and are worthy of further examination for possible treatment of COVID-19.

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Why the lower reported prevalence of asthma in patients diagnosed with COVID-19 validates repurposing EDTA solutions to prevent and manage treat COVID-19 disease

Cited by 9 publications

References 32 publications

Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort

Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort

SARS-CoV-2 envelope-protein corruption of homeostatic signaling mechanisms in mammalian cells

Inhibitors of L-Type Calcium Channels Show Therapeutic Potential for Treating SARS-CoV-2 Infections by Preventing Virus Entry and Spread

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