Friday Hope: Eugenol: Clove Oil and Tulsi: Inhibits Spike Binding to ACE2

Eugenol is also shown to inhibit Spike-induced NF-kB activation and to prevent Spike-induced arrhythmias.

If we have learned one thing about the Spike Protein, we have learned that stopping it in its tracks before it can do any harm is the best course of action we can take. To that end, I have been researching natural therapeutics which can help us achieve this goal. Fortunately, Nature has at least one such compound: Eugenol. Eugenol is found in Tulsi, Clove Oil and other natural sources. 

What is Eugenol? 

Eugenol /ˈjuːdʒɪnɒl/ is an allyl chain-substituted guaiacol, a member of the allylbenzene class of chemical compounds.[2] It is a colorless to pale yellow, aromatic oily liquid extracted from certain essential oils especially from clove, nutmeg, cinnamon, basil and bay leaf.[3][4][5][6] It is present in concentrations of 80–90% in clove bud oil and at 82–88% in clove leaf oil.[7] Eugenol has a pleasant, spicy, clove-like scent.[8] The name is derived from Eugenia caryophyllata, the former Linnean nomenclature term for cloves. The currently accepted name is Syzygium aromaticum. 

Eugenol 
https://en.wikipedia.org/wiki/Eugenol 

Indeed, the pharmacological uses of Eugenol are impressive and vast. 

Eugenol, the major constituent of clove oil, has been widely used for its anesthetic and analgesic action in dentistry. Eugenol exhibits pharmacological effects on almost all systems and our aim is to review the research work that has identified these pharmacological actions. Eugenol possesses significant antioxidant, anti-inflammatory and cardiovascular properties, in addition to analgesic and local anesthetic activity. The metabolism and pharmacokinetics of the compound in humans have been studied. Eugenol has also been used as a penetration enhancer. The compound is a very promising candidate for versatile applications, and the design of new drugs based on the pharmacological effects of eugenol could be beneficial. 

Pharmacological studies of eugenol and clove oil. 

Eugenol: A Natural Compound with Versatile Pharmacological Actions 
https://journals.sagepub.com/doi/epdf/10.1177/1934578X1000501236 

It also has very significant benefits when it comes to dealing with SARS-CoV-2 and its Spike Protein. It stops the Spike from interacting with ACE2. Access Denied! 

To confirm the binding of eugenol with spike S1, not ACE2, we employed thermal shift assay, which is an important tool for analyzing ligand-to-receptor binding. The melting profile of full-length spike S1 and human ACE2 was monitored with the aid of a SYBR Green reaction at 27-94 °C. Typical sigmoidal melting curves clearly indicated that recombinant spike S1 (Fig. 1D) and ACE2 (Fig. 1E) were conformationally stable. Interestingly, the melting assay revealed that 10 µM of eugenol was capable of strongly shifting the melting curve of spike S1 by 6 °C from 72.71 °C to 78.71 °C (Fig. 1D). In contrast, eugenol exhibited a thermal shift of only 0.7 °C with human ACE2 protein from 61.5 to 62.2 °C (Fig. 1E). In order to understand whether the complex of spike S1 and ACE2 was conformationally stable and whether eugenol was capable of influencing the preexisting complex, we examined the melting profile of the combination of spike S1 and ACE2 in the absence and presence of eugenol. As evident from sigmoidal melting curve, the complex of spike S1 and ACE2 was conformationally stable (Fig. 1F). However, the presence of eugenol led to a shift of the melting curve of the spike S1:ACE2 complex by 3.27 °C from 59.66 °C to 62.93 °C (Fig. 1F). Together, these results indicate that eugenol binds to SARS-CoV-2 spike S1, but not ACE2, and that eugenol is also capable of associating with the established spike S1:ACE2 complex. 

Yet, the benefits of Eugenol in fighting SARS-CoV-2 and its Spike Protein do not stop there. It also inhibits the activation of NF-kB, resulting in dramatically reduced cytokine expression. 

However, eugenol inhibited spike S1-induced activation of NF-κB (Fig. 3A). To confirm these results, we monitored the expression of TNFα, IL-1β and IL-6, proinflammatory cytokines that are driven by activated NF-κB. Spike S1 increased the expression of TNFα (Fig. 3B), IL-1β (Fig. 3C) and IL-6 (Fig. 3D) in A549 cells. However, eugenol dose-dependently inhibited SARS-CoV-2 spike S1-induced mRNA expression of TNFα (Fig. 3B), IL-1β (Fig. 3C) and IL-6 (Fig. 3D) in A549 cells. 

Furthermore, Eugneol was able to stabilize the heart’s electrical activity from interference by the Spike Protein, preventing arrythmias. 

Since many cardiac related problems of COVID-19 are modeled in SARS-CoV-2 spike S1-intoxicated mice (Paidi et al. 2021), we examined if oral eugenol was capable of improving heart functions in these mice. Non-invasive ECG demonstrated cardiac arrhythmias in SARS-CoV-2 spike S1-intoxicated mice as compared to control untreated mice (Fig. 5A, B). However, eugenol treatment normalized electrical activity of the heart as evident from ECG (Fig. 5A−C). Similarly, eugenol also steadied heart rate (Fig. 5D), heart rate variability (Fig. 5E), JT interval (Fig. 5F), ORS interval (Fig. 5G), QT interval (Fig. 5H), and RR interval (Fig. 5I) in SARS-CoV-2 spike S1-intoxicated mice. As expected, the level of LDH was also markedly higher in serum of SARS-CoV-2 spike S1-intoxicated mice than normal mice (Fig. 5J). However, eugenol treatment normalized serum LDH in spike S1-intoxicated mice (Fig. 5J). 

Eugenol, a Component of Holy Basil (Tulsi) and Common Spice Clove, Inhibits the Interaction Between SARS-CoV-2 Spike S1 and ACE2 to Induce Therapeutic Responses 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531902/ 

Clove Oil, Tulsi and other Eugenol-rich natural sources may be very helpful in preventing damage from and treating those with Acute COVID, Long COVID, Spike Protein pathologies, or those who have been exposed to the Spike Protein. 

One very important word of caution. Remember, this is a work of medical research and not medical advice. Eugenol can be toxic in high doses. Do not use any supplements or medications until you have consulted your Primary Care Provider.  

I am very encouraged by these findings. More studies need to be done, but the evidence so far suggests that Eugenol may be a powerful ally in dealing with COVID and Spike Protein-related pathologies. 

Thank you, as always, for your support, readership and dialogue. It is a rainy, tropical storm remnant weekend here in VT. A perfect time for some rest and contemplative reading. Wishing a peaceful and restful weekend to all.