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
Maiti et al.,
Active-site Molecular docking of Nigellidine to nucleocapsid/Nsp2/Nsp3/MPro of COVID-19 and to human IL1R and..,
Research Square, doi:10.21203/rs.3.rs-26464/v1 (Preprint)
In Silico and animal study of nigella sativa and component nigellidine, showing nigellidine binding activity for several important SARS-CoV-2 proteins and for relevant host receptors; and that black cumin seed extract was antioxidative, hepato- and reno-protective in rats.
Maiti et al., 5 May 2021, preprint, 5 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Preprint: Please note that this article has not completed peer review.
Active-site Molecular docking of Nigellidine to
nucleocapsid/Nsp2/Nsp3/MPro of COVID-19 and to
human IL1R and TNFR1/2 may stop viralgrowth/cytokine-flood, and the drug source Nigella
sativa (black cumin) seeds show potent antioxidant
role in experimental rats.
CURRENT STATUS:
POSTED
Smarajit Maiti
Oriental Institute of Science and Technology, Midnapore, India
maitism@rediffmail.comCorresponding Author
ORCiD: https://orcid.org/0000-0002-1354-1303
Amrita Banerjee
Oriental Institute of Science and Technology, Midnapore, India
Aarifa Nazmeen
Oriental Institute of Science and Technology, Midnapore, India
Mehak Kanwar
Oriental Institute of Science and Technology, Midnapore, India
Shilpa Das
Oriental Institute of Science and Technology, Midnapore, India
10.21203/rs.3.rs-26464/v1
SUBJECT AREAS
Bioinformatics
KEYWORDS
SARS CoV 2 proteins, cytokine, Nigellidine, inhibition, molecular docking, cytotoxicity
test, rat model.
1
Abstract
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 Nigella Sativa L.
(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 cuminseed 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), Nterminus-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 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.
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