Friday Hope: Nutmeg (Malabaricone C): Equal to or Better than Chloroquine and Hydroxychloroquine at Inhibiting SARS-CoV-2

In addition to possessing radioprotective (scavenging), anti-cancer and anti-inflammatory properties, a new study shows Malabaricone C as a stellar inhibitor of the Spike Protein.

Illustration of the fusion assay for SARS-CoV-2. Cell control (CC) was conducted with only assay medium. Virus control (VC) was conducted in the presence of SARS-CoV-2 without inhibitors. (A) Concept of the visualized fusion assay for SARS-CoV-2. The persistent cells were turned yellow and hypertrophied by cell fusion with two types of cells that introduced GFP and mCherry. (B) Scanning micrographs (× 40) of the fusion assay in the presence of each inhibitor at 12.5 μM after 24 h. (C) The fusion inhibition of Malabaricone C and its derivatives was measured by counting the number of yellow hypertrophy cells (> 500 μm2) (n = 2 biological replicates).

A paper published just weeks ago shows us, yet again, that Nature has provided us with therapeutics that rival some of our most established pharmaceuticals. Today we will discuss Malabaricone C. I am extremely impressed with the multiple anti-Spike abilities of this compound.

What is Malabaricone C?

Malabaricone C is an antimicrobial resorcinol found in nutmeg, the dried seed covers of Myristica fragrans and Myristica malabarica (rampatri). This Compound exhibits strong antifungal and antibacterial activity. (PMID 1955885 , 10501006 ). Malabaricone C a diarylnonanoid, shows strong scavenging activity. (PMID 16104820 ).

Malabaricone C belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.

Showing metabocard for Malabaricone C (HMDB0005798)
https://hmdb.ca/metabolites/HMDB0005798

Addressing our immediate concerns of inhibiting the Spike Protein, Malabaricone C (MC) was recently shown to possess the ability to perform this inhibitory task as well as or better than Chloroquine and Hydroxychloroquine. Imagine if we had used this compound from the very outset. Instead, we had Rundeathisnear coerced up us...

The above finding gives me great hope, especially as it prevents Spike fusion by modulating lipid raft formation. The authors point out that this may have beneficial effects for other viral infections, as well.

In particular, malabaricone C and compounds (3), (4), and (6) had a large selective index of over five values between EC50 and CC50. Interestingly, those compounds exhibited potent antiviral effect against SARS-CoV-2 variants with an EC50of 1.5–2.0 μM, and their antiviral activities were equal to or even more potent than those of chloroquine and hydroxychloroquine, the anti-SARS-CoV-2 drugs that have been FDA-approved for COVID-19 treatment373839...

Here, we first demonstrated the partial mechanism of the anti-SARS-CoV-2 activity of malabaricone via interference with lipid raft formation on the plasma membrane in Vero E6 cells.

Malabaricone C isolated from edible plants as a potential inhibitor of SARS-CoV-2 infection
https://www.nature.com/articles/s41598-024-83633-8

Looking further under the hood of MC, it offers other protections from the ravages of the Spike Protein. Perhaps the most important being its ability to protect DNA and scavenge free radicals.

Malabaricone C could prevent both Fe(II)- and 2,2'-azobis(2-amidinopropane)dihydrochloride-induced lipid peroxidation (LPO) of rat liver mitochondria more efficiently than curcumin. The anti-LPO activity of malabaricone C was attributed to its better radical scavenging and Fe(II) chelation capacities. The superior activity of malabaricone C was rationalized by a systematic structure-activity correlation of the results obtained with the structurally related diarylnonanoids and curcumin. Malabaricone C also prevented the gamma-ray-induced damage of pBR322 plasmid DNA in a concentration-dependent manner. The radioprotective activity was found to correlate with its (*)OH radical scavenging property, which matched well with that of d-mannitol.

Antioxidant activity of Myristica malabarica extracts and their constituents
https://pubmed.ncbi.nlm.nih.gov/16104820/

Those that have Diabetes have been at increased risk of severe COVID. Leukotriene B4-driven inflammation is present in those with Diabetes and exacerbated by SARS-CoV-2.

We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (ACE2/TMPRSS2), and for the main molecule of the leukotriene B4 (LTB4) pathway (ALOX5). We found that diabetes activates the LTB4 pathway and that during COVID-19 it increases ACE2/TMPRSS2 as well as ALOX5 expression. Diabetes was also associated with COVID-19–related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO2) and arterial partial pressure of oxygen/FiO2 levels, and increased disease duration. In addition, the expressions of ACE2 and ALOX5 are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB4 is significantly increased in individuals with diabetes.

LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes
https://pmc.ncbi.nlm.nih.gov/articles/PMC8576416/

MC may be beneficial for those with Diabetes who have COVID, Long COVID and/or Spike Protein injury/disease as MC decreases levels of LTB-4.

Malabaricone C exhibited potent competitive inhibition of 5-lipoxygenase with an IC50 value of 0.2 μM. In mice with imiquimod-induced psoriasis-like skin lesions, topical application of 2 mM malabaricone C significantly ameliorated hyperplasia and inflammatory cell infiltration, and suppressed the expression of the psoriasis-associated genes S100a9, Krt1, Il17a, and Il22. Lipid metabolome analysis of these psoriasis-like skin lesions showed that malabaricone C markedly decreased the level of leukotriene B4 but did not significantly increase the other pro-inflammatory lipid mediators. These findings suggest that malabaricone C decreases LTB4 by the 5-lipoxygenase inhibition and ameliorates the symptoms of psoriasis-like skin inflammation.

Malabaricone C derived from nutmeg inhibits arachidonate 5-lipoxygenase activity and ameliorates psoriasis-like skin inflammation in mice
https://www.sciencedirect.com/science/article/abs/pii/S0891584922006189

Clinicians may wish to offer MC to their patients with COVID, Long COVID and/or Spike Protein injury/disease. It may be able to help restore health to your patients. Additional studies should be conducted with MC on larger scales with those affected in any way by SARS-CoV-2 and its Spike Protein.

Of course, this is a work of medical research and not medical advice. Please always consult your Primary Care Provider before using any medication or supplement.

I must say, Béchamel sauce is looking particularly appealing this weekend! It is warming up here in northern Vermont and you can feel the earth awakening. Mahler III always comes to mind for me this time of year. Thank you, as always, for your continued support, dialogue and readership. Discoveries such as the one we looked at today make it worth every effort. Also, a heartfelt Thank You to the Subscriber who sent me a very generous donation this week. Please have a blessed and hopeful weekend.