A Nicotinic Hypothesis For Covid-19 With Preventive And Therapeutic Implications

[Jam]

Abstract
SARS-CoV-2 epidemics raises a considerable issue of public health at the planetary scale. There is a pressing urgency to find treatments based upon currently available scientific knowledge. Therefore, we tentatively propose a hypothesis which hopefully might ultimately help saving lives. Based on the current scientific literature and on new epidemiological data which reveal that current smoking status appears to be a protective factor against the infection by SARS-CoV-2 [1], we hypothesize that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection.

 

[revenant]

Nice find.

 

[YourUniverse]

They think nicotine helps prevent covid?

 

[Terma]

Interestingly, ivermectin, which has been recently shown to inhibit the replication of SARS-CoV-2 in cells in vitro [53], is a positive allosteric modulator of a7 nAChR [54].

 

[Jam]

Good catch @Terma

Also:
French researchers to test nicotine patches on coronavirus patients

 

[zewe]

COVID-19, ACE2, Nicotinic Receptors And The Cholinergic Anti-Inflammatory And Cognitive-Improving Pathway -- Sott.net

 

[LeeLemonoil]

A very good article by this Gabriela Segura, MD

EDIT: many great articles by Segura. Didn’t know her. Pls subscribe / support

 

[LUH 3417]

Cigarettes make me go to the bathroom. Probably less endotoxin for smokers.

 

[Terma]

Didn't have time to read these properly

The effect of peripherally administered CDP-choline in an acute inflammatory pain model: the role of alpha7 nicotinic acetylcholine receptor. - PubMed - NCBI

BACKGROUND:
CDP-choline (citicholine; cytidine-5'-diphosphate choline) is an endogenously produced nucleotide which, when injected intracerebroventricularly, exerts an antinociceptive effect in acute pain models mediated by central cholinergic mechanisms and alpha7 nicotinic acetylcholine receptors (alpha7nAChR). Previous reports also suggest that the peripheral cholinergic system has an antiinflammatory role mediated by alpha7nAChRs on macrophages.

METHODS:
We used male Sprague-Dawley rats to assess the antihypersensitivity and antiinflammatory effect of CDP-choline after intraplantar injection of carrageenan (100 microL, 2%). Mechanical paw withdrawal thresholds and paw thickness were measured by Randall-Selitto testing and microcallipers, respectively. All drugs were administered intraplantarly in a volume 50 microL.

RESULTS:
CDP-choline (1, 2.5, 5 micromol; intraplantar) increased the mechanical paw withdrawal threshold and decreased paw edema in a dose- and time-dependent manner in the carrageenan-injected hindpaw. CDP-choline administration to the noninflamed contralateral hindpaw did not alter ipsilateral inflammation. Methyllycaconitine (100 nmol), a selective alpha7nAChR antagonist, completely blocked the effects of CDP-choline when administered to the inflamed hindpaw. However, the administration of methyllycaconitine to the contralateral hindpaw did not block the effects of CDP-choline in the ipsilateral paw. The administration of CDP-choline (5 micromol) 10 min after carrageenan administration to the ipsilateral hindpaw did not reduce swelling and edema but did significantly reduce hypersensitivity. Treatment with CDP-choline decreased tumor necrosis factor-alpha production in the rat paw tissue after carrageenan.

CONCLUSIONS:
The results of this study suggest that intraplantar CDP-choline has antihypersensitivity and antiinflammatory effects mediated via alpha7nAChRs in the carrageenan-induced inflammatory pain model.

Combining CDP-choline and galantamine: Effects of a selective α7 nicotinic acetylcholine receptor agonist strategy on P50 sensory gating of speech ... - PubMed - NCBI

BACKGROUND:
Schizophrenia (SCZ) patients and relatives have deficits in early cortical sensory gating (SG) typically measured by suppression of electroencephalography-derived P50 event-related potentials (ERPs) in a conditioning-testing (S1-S2) paradigm. Associated with alpha 7 nicotinic acetylcholine receptor (α7 nAChR) dysfunction and shown to be improved with nicotine and α7 nAChR agonists, SG has recently been shown to be improved in low P50 suppressing SCZ patients following acute CDP-choline treatment.

AIMS:
This pilot study in healthy humans assessed the SG effects of an α7 nAChR strategy combining CDP-choline with galantamine, a positive allosteric modulator (PAM) of nAChRs, aimed at increasing and prolonging nicotinic receptor activity.

METHODS:
The combined effect of CDP-choline (500 mg) and galantamine (16 mg) on speech P50 gating indices rP50 (S2/S1) and dP50 (S1-S2) was examined in 30 healthy participants stratified into low and high baseline P50 suppressors in a randomized, double-blind, placebo-controlled and counterbalanced design.

RESULTS:
In low suppressors, CDP-choline/galantamine (vs. placebo) improved rP50 and dP50 gating, and reduced S2P50 amplitudes. No P50 gating effects were observed in high suppressors; however, CDP-choline/galantamine (vs. placebo) increased their S2P50 amplitudes.

CONCLUSION:
Findings from this pilot study with CDP-choline/galantamine in a healthy, SCZ-like surrogate deficient gating sample are consistent with the association of α7 nAChR mechanisms in SG impairment in SCZ and support further research trials with CDP-choline and galantamine targeting sensory processes.

PLA2 + Coronavirus COVID-19 — The Great Plains Laboratory, Inc. (sounds shady?)

PLA2 and Viruses
Several studies show that some very serious viral infections, including Coronavirus, Parvovirus, Cytomegalovirus, and West Nile Virus all require the PLA2-activated cascade to do the most cell damage, so reducing your PLA2 levels may truly help fight these viruses and minimize the impact they have on your health. Here are links to some of these studies:

Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication

Inhibition of Cytosolic Phospholipase A2α Impairs an Early Step of Coronavirus Replication in Cell Culture

A Viral Phospholipase A2 Is Required for Parvovirus Infectivity

Phospholipase A2 Activity During the Replication Cycle of the Flavivirus West Nile Virus

Viral Escape from Endosomes and Host Detection at a Glance

Possible Role of Lysolecithins and Nonesterified Fatty Acids in the Pathogenesis of Reye’s Syndrome, Sudden Infant Death Syndrome, Acute Pancreatitis, and Diabetic Ketoacidosis

What Reduces PLA2?
Cytidine 5-diphospho-choline (CDP-choline), a precursor in the formation of phospholipids, is a potent inhibitor of PLA2 that has been used as a nutritional supplement at doses ranging from 500-4000 mg per day in the treatment of patients with a variety of disorders including Parkinson's disease, memory disorders, vascular cognitive impairment, vascular dementia, senile dementia, schizophrenia, Alzheimer's disease (especially effective in those with the epsilon-4 apolipoprotein E genotype), head trauma, and ischemic stroke. A trial in patients with Alzheimer's disease indicated that citicoline (1,000 mg/day) is well tolerated and improves cognitive performance, cerebral blood perfusion, and the brain bioelectrical activity pattern. No side effects were noticed at the lower doses of CDP-choline and only some mild gastrointestinal symptoms were found using higher doses. No abnormal blood chemistry or hematology values were found after the use of CDP-choline. If you’re looking for more information on CDP-choline please fill out this form and we will quickly respond.

Glucocorticoids such as the natural hormone cortisol and pharmaceutical agents such as dexamethasone inhibit the production of phospholipase, decreasing harm caused by the enzyme but also decreasing the benefits of the enzyme in killing harmful microorganisms. Thus, excess glucocorticoids can reduce inflammation in a patient with tuberculosis while reducing the effects of PLA2 against the bacteria resulting in spread of the illness. Lithium at pharmacological doses, carbamazepine, and the antimalarial drug chloroquine are all PLA2 inhibitors. Vitamin E is also an inhibitor of PLA2. In addition, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (belonging to the omega-3 class of fatty acids) inhibit PLA2.

 

[ddjd]

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