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
Abstract
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 blood-pressure/vascular-health of the individuals
which is demolished in Covid-19 infection manifesting
aldosterone/salt-deregulations/inflammations/endothelial-dysfunctions/hyper-hypo-
tension, sepsis/hypovolemic-shock and vessel-thrombosis/coagulations.
These cause comorbidity patients. Here, nigellidine, an
indazole-alkaloid was analyzed by molecular-docking for binding to
different Angiotensin-binding-proteins (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 proper-binding 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 effectively blocked
by nigellidine. The ACEs-blocking could restore Angiotensin-level and
restrict vaso-turbulence in Covid-infected patients and
receptor-blocking might stop inflammatory/vascular impairment. Further,
nigellidine may slowdown the vaso-fluctuations due to Angiotensin
deregulations in Covid-infected patients. Angiotensin II-ACE2 binding
(ACE-value -294.81) is more favorable than nigellidine-ACE2. Contrarily,
nigellidine-ACE1 binding-energy/Ki are lower than nigellidine-ACE2
values indicating a balanced-state between constriction-dilatation. It
is also noticed that nigellidine binds to the viral-spike, closer
proximity to its ACE2 binding-domain. Taken together,
Covid-infected-patients/elderly-patients/comorbid-patients (with
hypertensive/diabetic/cardiac/renal impairment, counting
>90% of non-survivors) could be greatly benefited.