NIGELLIN®THYMOQUINONE

NIGELLA SATIVA AND THYMOQUINONE

Having a range of bioactive components such as thymoquinone and nigellimine, black seed might offer a number of benefits to treat COVID-19 such as (i) blocking the entry of the virus into pneumocytes and (ii) providing ionophore for enhanced uptake of Zn2+ which in turn can enhance host immune response against SARS-CoV-2 as well as inhibit its replication by blocking the viral RdRp. (Rahman, 2020).

Molecular docking of compounds from N sativa and some antiviral drugs was performed to determine their binding affinity with SARS-CoV-2–related molecular targets such as main proteases (6LU7 and 6Y2E), main peptidase (2GTB), angiotensin converting enzyme 2 (ACE2), and heat shock protein A5. The binding of some natural compounds might prevent the adhesion of coronavirus to host epithelial cells. Nigelledine, an alkaloid in N sativa, docked with 6LU7 active sites showed an energy complex score close to chloroquine and better than hydroxychloroquine and favipiravir. α-Hederin, a saponin in N sativa, docked with 2GTB active sites showed an energy score better than chloroquine, hydroxychloroquine, and favipiravir.

Thymoquinone, the main essential oil constituent of N sativa, had a binding affinity with 6LU7, ACE2, and heat shock protein A5 active sites with a score less than hydroxychloroquine in 6LU7 and ACE2. Also, hederagenin, a saponin in N sativa, docked with 6LU7, 6Y2E, ACE2, and GRP78 active sites showed a binding score less than saquinavir in 6LU7 and 6Y2E. Thymohydroquinone showed moderate docking energy with SARS-CoV-2 6LU7, endoribonucleoase, ADP-ribose-1″−phosphatase, RNA-dependent RNA polymerase, the binding domain of the SARS-CoV-2 spike protein, and human ACE2. Nigellidine showed high binding affinity SARS-CoV-2 enzymes and proteins such as N- terminus-protenase, 6LU7, nonstructural protein 2, spike-glycoprotein, and nucleocapsid. Nigellidine had high binding energy with human receptors, inflammatory signal molecules, and other proteins such as human IL1R (1itb), TNFR1 (1ncf), and TNFR2 (3alq).

Therefore, certain natural compounds found in N sativa such as nigellidine, α-hederin, hederagenin, thymohydroquinone, and thymoquinone were potentially active compounds that might inhibit coronavirus. (Koshak, 2020).

Using both black seed-extracted Thymoquinone (THQ) and commercially available pure THQ, we provide evidence for the first time that THQ possesses anticoagulant activity, as determined by in vitro coagulation assays. Both pure THQ and black seed-extracted-THQ modulate normal blood coagulation with minimal effect in a narrow dose range. In contrast, pure THQ can effectively reverse coagulation to basal levels when triggered by TF present on pancreatic cancer cells and by lipopolysaccharide (LPS). We also performed mechanistic studies and confirm that THQ decreases blood coagulation directly by decreasing factor Xa inactivation in blood coagulation cascade and by interfering with the crosstalk between inflammation and thrombosis. (Muralidharan, 2016).

Reference:

(Rahman, 2020). Rahman MT. Potential benefits of combination of Nigella sativa and Zn supplements to treat COVID-19. J Herb Med. 2020;23:100382. doi:10.1016/j.hermed.2020.100382. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313527/

(Koshak, 2020). Koshak DAE, Koshak PEA. Nigella sativa L as a potential phytotherapy for coronavirus disease 2019: A mini review of in silico studies. Curr Ther Res Clin Exp. 2020;93:100602. doi:10.1016/j.curtheres.2020.100602.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445151/

(Muralidharan, 2016). Muralidharan-Chari V, Kim J, Abuawad A, Naeem M, Cui H, Mousa SA. Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory and Coagulation Pathways. Int J Mol Sci. 2016;17(4):474. Published 2016 Mar 30. doi:10.3390/ijms17040474