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

{ 'indexed': {'date-parts': [[2023, 5, 15]], 'date-time': '2023-05-15T14:59:31Z', 'timestamp': 1684162771854}, 'posted': {'date-parts': [[2020, 5, 5]]}, 'group-title': 'In Review', 'reference-count': 0, 'publisher': 'Research Square Platform LLC', 'license': [ { 'start': { 'date-parts': [[2020, 5, 5]], 'date-time': '2020-05-05T00:00:00Z', 'timestamp': 1588636800000}, 'content-version': 'unspecified', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2020, 5, 2]]}, '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>', 'DOI': '10.21203/rs.3.rs-26464/v1', 'type': 'posted-content', 'created': {'date-parts': [[2020, 5, 5]], 'date-time': '2020-05-05T20:59:00Z', 'timestamp': 1588712340000}, 'source': 'Crossref', 'is-referenced-by-count': 7, '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.', 'prefix': '10.21203', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-1354-1303', 'authenticated-orcid': False, 'given': 'Smarajit', 'family': 'Maiti', 'sequence': 'first', 'affiliation': [{'name': 'Oriental Institute of Science and Technology, Midnapore, India'}]}, { 'given': 'Amrita', 'family': 'Banerjee', 'sequence': 'additional', 'affiliation': [{'name': 'Oriental Institute of Science and Technology, Midnapore, India'}]}, { 'given': 'Aarifa', 'family': 'Nazmeen', 'sequence': 'additional', 'affiliation': [{'name': 'Oriental Institute of Science and Technology, Midnapore, India'}]}, { 'given': 'Mehak', 'family': 'Kanwar', 'sequence': 'additional', 'affiliation': [{'name': 'Oriental Institute of Science and Technology, Midnapore, India'}]}, { 'given': 'Shilpa', 'family': 'Das', 'sequence': 'additional', 'affiliation': [{'name': 'Oriental Institute of Science and Technology, Midnapore, India'}]}], 'member': '8761', 'container-title': [], 'original-title': [], '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'}], 'deposited': { 'date-parts': [[2020, 9, 3]], 'date-time': '2020-09-03T21:43:42Z', 'timestamp': 1599169422000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.researchsquare.com/article/rs-26464/v1'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2020, 5, 5]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.21203/rs.3.rs-26464/v1', 'relation': {}, 'subject': [], 'published': {'date-parts': [[2020, 5, 5]]}, 'subtype': 'preprint'}