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

Abstract

Spike S1 of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells to enter the cell and initiate COVID-19. Since ACE2 is a favorable enzyme, we were interested in finding a molecule capable of binding spike S1, but not ACE2, and inhibiting the interaction between spike S1 and ACE2. Holy basil (Tulsi) has a long history as a medicine for different human disorders. Therefore, we screened different components of Tulsi leaf and found that eugenol, but not other major components (e.g. ursolic acid, oleanolic acid and β-caryophylline), inhibited the interaction between spike S1 and ACE2 in an AlphaScreen-based assay. By in silico analysis and thermal shift assay, we also observed that eugenol associated with spike S1, but not ACE2. Accordingly, eugenol strongly suppressed the entry of pseudotyped SARS-CoV-2, but not vesicular stomatitis virus (VSV), into human ACE2-expressing HEK293 cells. Eugenol also reduced SARS-CoV-2 spike S1-induced activation of NF-κB and the expression of IL-6, IL-1β and TNFα in human A549 lung cells. Moreover, oral treatment with eugenol reduced lung inflammation, decreased fever, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of SARS-CoV-2 spike S1, but not ACE2, by eugenol may be beneficial for COVID-19 treatment.

An exhaustive comprehension of the role of herbal medicines in Pre- and Post-COVID manifestations

“…In silico and thermal shift assays reported that the eugenol is associated with spike S1, but it did not have any impact on ACE2. Consequently, eugenol strongly suppressed the entry of pseudo typed SARS-COV-2 and decreased SARS-COV-2 spike S1-induced activation of NF-κB and in the human A549 lung cells, the expression of IL-6, IL-1β, and TNFα was also found to be reduced, confirming its potential for selective targeting of spike S1 of SARS-COV-2 ( Paidi et al, 2021 ).…”

“…Further, similar dosing of tulsi has shown a potent antiviral effect by avoiding the entry of the virus into the cell. In other research, Paidi et al (2021) screened the various component of the tulsi leaf. By the Alpha Screen assay, it was observed that the eugenol significantly inhibited the interaction between spike S1 and ACE2.…”

Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study

“… 23 , 33 The mechanism by which carnation may reduce the severe form of COVID-19 involves interference of SARS-CoV-2 S1-protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor. 34 Moreover, carnation has been shown to increase the availability of oxygen by improving blood supply to both the heart and the brain. 35 Carnation has also been reported to be beneficial for the management of chronic coughs, shortness of breath, and maintaining a normal heart rate.…”

The Neuroimmune Pharmacology of SARS-CoV-2

“…Disruption to binding between ACE2 and spike S1 could be therapeutically beneficial. Based on their ongoing studies, Dr. Pahan’s lab, explored and identified Eugenol, a component of holy basil (Tulsi), capable of binding spike S1, but not ACE2, and inhibiting the interaction between spike S1 and ACE2 (Paidi et al 2021 ). Using an AlphaScreen-based assay, only Eugenol, but not other major components of Tulsi leaf, was found to block the interaction between spike S1 and ACE2.…”

“…Next comes the issue’s review paper, “Racial Health Disparity and COVID-19” (Kumar et al 2021b ) followed by three original research articles. One of these primary research papers examines a potential treatment approach using the herbal product, “Eugenol, a component of holy basil (Tulsi) and common spice clove, and reporting that this herbal product inhibits the interaction between SARS-CoV-2 spike S1 and ACE2 to induce therapeutic responses” (Paidi et al 2021 ). The next paper describes original meta-analysis research, “Network meta-analysis on the changes of amyloid precursor protein expression following SARS-CoV-2 infection” (Camacho et al 2021 ).…”