Active-site Molecular docking of Nigellidine to nucleocapsid/Nsp2/Nsp3/MPro of COVID-19 and to human IL1R and TNFR1/2 may stop viral-growth/cytokine-flood, and the drug source Nigella sativa (black cumin) seeds show potent antioxidant role in experimental rats

DOI record: { "DOI": "10.21203/rs.3.rs-26464/v1", "URL": "http://dx.doi.org/10.21203/rs.3.rs-26464/v1", "abstract": "<jats:title>Abstract</jats:title>\n <jats:p>The recent outbreak of SARS CoV-2 has changed the global scenario of human lives and economy. In this pandemic-outbreak the ratio of infected person is much higher than the death encountered. Most of the dead patients were observed with dysfunction/failure of cardiac and renal systems. Beside this a ‘cytokine storm’ namely TNF-α/IL1 receptors i.e. TNFR1/TNFR2/IL1R over-functioning was reported in the infected-persons. Here, nigellidine, an indazole-alkaloid and key-component of <jats:italic>Nigella Sativa L</jats:italic>. (NS); black-cumin-seed, has been analyzed for COVID-19 different protein and TNFα receptors TNFR1/TNFR2 and IL1R inhibition through molecular-docking study and biochemical-study of cumin-seed extract exposure to experimental-rat. The NMR, X-ray-crystallographic or Electron-microscopic structures of COVID-19 Main-protease(6LU7), Spike-glycoprotein(6vsb), NSP2(QHD43415_2), N-terminus-protenase (QHD43415_3), Nucleocapsid(QHD43423) and Human IL1R (1itb), TNFR1 (1ncf), TNFR2 (3alq) from PDB were retrieved/analyzed for receptor-ligand interaction in normal condition. Then those structures were docked with nigellidine using Autodock-software and Patchdock-server. Where nigellidine showed highest binding-energy of -7.61 (kcal/mol) and ligand-efficiency value of (-0.35) forming bonds with amino acids THR943/LYS945/MET1556/ALA1557/PRO1558/ILE1559. Highest ACE-value of -356.72 was also observed for nigellidine N-terminal-protease interaction. Nigellidine also showed strong interaction with NSP2 (-6.28) and Mpro/3CLpro_Q (-6.38s). Nigellidine showed affinity to TNFR1 (-6.81), IL1R (-6.23) and TNFR2 (-5.16). In rat experiment 2-groups (vehicle and NS treated) of female Wistar-rats were taken for experiments. The NS treated tissue showed marked decline in ALP/SGPT/ SGOT/MDA level then the basal-levels. From the Western-blot or activity analysis<jats:italic> </jats:italic>it was observed that Nigellidine, the sulfuryl-group containing drug showed no impact on Phenol-catalyzing ASTIV or Steroid-catalyzing EST expressions/activities and thus have no influence in sulfation-mediated adverse metabolic-processes. Current-results concluded that Nigellidine has hepato/reno-protective; immunomodulatory/anti-inflammatory and antioxidant activities as well as it inhibits important proteins of COVID-19. With steps to further validation/checking nigellidine can be used in COVID-19 infection.</jats:p>", "accepted": { "date-parts": [ [ 2020, 5, 2 ] ] }, "author": [ { "ORCID": "http://orcid.org/0000-0002-1354-1303", "affiliation": [ { "name": "Oriental Institute of Science and Technology, Midnapore, India" } ], "authenticated-orcid": false, "family": "Maiti", "given": "Smarajit", "sequence": "first" }, { "affiliation": [ { "name": "Oriental Institute of Science and Technology, Midnapore, India" } ], "family": "Banerjee", "given": "Amrita", "sequence": "additional" }, { "affiliation": [ { "name": "Oriental Institute of Science and Technology, Midnapore, India" } ], "family": "Nazmeen", "given": "Aarifa", "sequence": "additional" }, { "affiliation": [ { "name": "Oriental Institute of Science and Technology, Midnapore, India" } ], "family": "Kanwar", "given": "Mehak", "sequence": "additional" }, { "affiliation": [ { "name": "Oriental Institute of Science and Technology, Midnapore, India" } ], "family": "Das", "given": "Shilpa", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2020, 5, 5 ] ], "date-time": "2020-05-05T20:59:00Z", "timestamp": 1588712340000 }, "deposited": { "date-parts": [ [ 2020, 9, 3 ] ], "date-time": "2020-09-03T21:43:42Z", "timestamp": 1599169422000 }, "group-title": "In Review", "indexed": { "date-parts": [ [ 2023, 5, 15 ] ], "date-time": "2023-05-15T14:59:31Z", "timestamp": 1684162771854 }, "is-referenced-by-count": 7, "issued": { "date-parts": [ [ 2020, 5, 5 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "unspecified", "delay-in-days": 0, "start": { "date-parts": [ [ 2020, 5, 5 ] ], "date-time": "2020-05-05T00:00:00Z", "timestamp": 1588636800000 } } ], "link": [ { "URL": "https://www.researchsquare.com/article/rs-26464/v1", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.researchsquare.com/article/rs-26464/v1.html", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "8761", "original-title": [], "posted": { "date-parts": [ [ 2020, 5, 5 ] ] }, "prefix": "10.21203", "published": { "date-parts": [ [ 2020, 5, 5 ] ] }, "publisher": "Research Square Platform LLC", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "https://www.researchsquare.com/article/rs-26464/v1" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "subtype": "preprint", "title": "Active-site Molecular docking of Nigellidine to nucleocapsid/Nsp2/Nsp3/MPro of COVID-19 and to human IL1R and TNFR1/2 may stop viral-growth/cytokine-flood, and the drug source Nigella sativa (black cumin) seeds show potent antioxidant role in experimental rats.", "type": "posted-content" }