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 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 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

The naturally‐derived alkaloids as a potential treatment for COVID‐19: A scoping review

“…Overall, 11 studies (25.58%) approached the spike glycoprotein as target protein, being the alkaloids analyzed the following: crambescidin 826, cryptospirolepine, deoxynortryptoquivaline, ergotamine, hyoscyamine, nicotine docking on soluble angiotensin‐converting enzyme II receptor in complex with spike (S) protein of Indian SARS‐CoV‐2 (sACE2‐INS1), nigellidine, norbolidine, pallidine, piperine and quinadoline B (Borquaye et al, 2020 ; El‐Demerdash et al, 2021 ; Firdiana et al, 2021 ; Gyebi et al, 2020 ; Ismail et al, 2021 ; Selvaa Kumar, Kumar, & Wei, 2020 ; Maiti, Banerjee, & Kanwar, 2021 ; Maiti, Banerjee, Nazmeen, Kanwar, & Das, 2020 ; Mao, Bie, Xu, Wang, & Gao, 2021 ; Ogunyemi et al, 2020 ; Skariyachan, Gopal, Muddebihalkar, & Uttarkar, 2021 ).…”

“…The alkaloids nicotine, nigellidine, norboldine, piperine, quinadoline A and trytoquivaline showed binding capacity to the angiotensin‐converting enzyme II (ACE2) (Firdiana et al, 2021 ; Ismail et al, 2021 ; Maiti et al, 2021 ; Maurya, Kumar, Prasad, Bhatt, & Saxena, 2020 ; Selvaa Kumar, Kumar, & Wei, 2020 ).…”

“…This herb is extensively employed traditional medicine like Ayurveda and Unani due to its extract safety, anti‐oxidant, anti‐bacterial, anti‐inflammatory, anti‐hypertensive activity and immunomodulatory effects. Therefore, this compound found in N. sativa has been associated with high energy binding with spike glycoprotein, NSP2, nucleocapsid N, ACE1, ACE2, AT1, AT2, in addition to having strong interactions with Mpro (Maiti et al, 2020 , 2021 ). Renal and hepatic toxicities of the alkaloid nigellidine were evaluated in female Wistar rats, revealing no important safety concerns for the use of this substance (Maiti et al, 2020 ).…”

Effects of theaflavin-gallate in-silico binding with different proteins of SARS-CoV-2 and host inflammation and vasoregulations referring an experimental rat-lung injury

“…Our previous report on the similarities in the angiotensin binding proteins i.e. ACE, ACE2, AT1, AT2has explained this issues ( Maiti et al, 2021 ). In this investigation TFMG has been shown to bind some common amino acids in the active sites of angiotensin regulating proteins ( Fig.…”