In silico Nigellidine (N. sativa) bind to viral spike/active-sites of ACE1/2, AT1/2 to prevent COVID-19 induced vaso-tumult/vascular-damage/comorbidity [post]

Smarajit Maiti, Amrita Banerjee, Mehak Kanwar
2020 unpublished
COVID-19 is the global-pandemic targets human-lung-ACE2 that converts Angiotensin-II to (1-7) peptide causing vasodilatation. Vasoconstriction caused by Angiotensin-II is produced from Angiotensin-I by ACE1. The vaso-status maintains bloodpressure/vascular-health of the individuals which is demolished in Covid-19 infection manifesting aldosterone/salt-deregulations/inflammations/endo dysfunctions/hyper-hypo-tension, sepsis/hypovolemic-shock and vessel-thrombosis/coagulations. These cause
more » ... These cause comorbidity patients. Here, nigellidine, an indazole-alkaloid was analyzed by molecular-docking for binding to different Angiotensin-bindingproteins (enzymes, ACE1(6en5)/ACE2(4aph)/receptors, AT1(6os1)/AT2(5xjm)) and COVID-19 spike-glycoprotein(6vsb). Data suggest that nigellidine strongly binds to the spike-protein at the hinge-region/active-site-opening which may hamper properbinding of nCoV2-ACE2 surface. Nigellidine strongly (-7.54 kcal/mol, -211.76, Atomic-Contact-Energy; ACE-value) binds (>known-binderEGCG; -4.53 and Theaflavin-di-gallate; -2.85) in the Angiotensin-II binding-site/entry-pocket at ACE2 with Ki 8.68 and 8.3 μmol. Further, Nigellidine showed strong-binding (best Ki, 50.93μmol/binding-energy -5.48 kcal/mol) to both mono-and multi-meric ACE1-forms. Moreover, this compound binds Angiotensin-receptors, AT1/AT2 (Ki, 42.79/14.22 μmol, binding-energy, -5.96/-6.61 kcal/mol) at active-sites, respectively. Here, we first-time report that nigellidine can block all angiotensin-binding proteins where, the Angiotensin-bonded amino acids were more or less similar/analogous and effec-
doi:10.22541/au.159421867.79066783 fatcat:jqy7er7oxrcepopeiuz5kz4f5e