Holy basil (Tulsi) has a long history as a medicine for different human disorders. Hence the study team 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.
Utilizing silico analysis and thermal shift assay, the study team also observed that eugenol associated with spike S1, but not ACE2.
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.
Importantly, oral treatment with eugenol reduced lung inflammation, decreased fever, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice.
The study findings were published in the peer reviewed Journal of Neuroimmune Pharmacology. https://link.springer.com/article/10.1007/s11481-021-10028-1
Holy basil or Tulsi (Ocimum tenuiflorum) is cultivated in Southeast Asia for religious and traditional medicine purposes (Cohen 2014). Tulsi is known to augment immunity that may help fight viral, bacterial and fungal infections.
For example, in a 4-week study in 24 healthy individuals, it has been found that supplementation of 300 mg of holy basil extract is capable of increasing levels of IFN-γ, IL-4 and percentages of T-helper cells and natural killer cells (Mondal et al. 2011).
These are the immune cells that are beneficial in protecting and defending the human body from viral infections. In addition, many cell culture and animals studies have delineated anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, radioprotective, anxiolytic, adaptogenic, metabolic, and anti-diabetic effects of Tulsi leaf (Prakash and Gupta 2005; Baliga et al. 2013; Cohen 2014; Jamshidi and Cohen 2017).
The coronavirus disease 2019 (COVID-19) pandemic that started from the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 is still continuing to kill thousands of people daily worldwide.
Severity to COVID-19 increases with age as well as preexisting conditions, such as hypertension, obesity, asthma, or diabetes. It has been found that severely ill COVID-19 patients suffer from cytokine storm, lung injury and multi-organ failure (Pia 2020).
Although underlying mechanisms are poorly understood, COVID-19 is more lethal in men than it is in women (Mukherjee and Pahan 2021). While vaccination is underway and more than 50 % people in USA are fully vaccinated, a specific and an effective antiviral and anti-inflammatory agent is also needed to treat this viral pandemic.
Angiotensin-converting enzyme 2 (ACE2) is a beneficial molecule as it converts angiotensin II (AngII), a vasoconstrictor, to Ang1-7, a vasodilator (Vickers et al. 2002; Zaman et al. 2002). Since the spike protein on the surface of SARS-CoV-2 binds to ACE2 (Machhi et al. 2020; Stower 2020) to enter into human cells and the spike S1 subunit harbors the receptor-binding domain (RBD), we screened different components of Tulsi leaf and found that eugenol was capable of inhibiting the interaction between spike S1 and ACE2.
In addition, eugenol inhibited the entry of pseudotyped SARS-CoV-2, but not VSV, into human ACE2-expressing HEK293 cells and suppressed spike S1-induced activation of NF-κB and expression of proinflammatory cytokines in human lungs cells. Oral administration of eugenol also decreased lung inflammation, reduced fever, inhibited arrhythmias, and enhanced locomotor activities in an animal model of COVID-19, indicating that naturally available eugenol may be beneficial for COVID-19.
