Active-site Molecular docking of Nigellidine with nucleocapsid- NSP2-MPro of COVID-19 and to human IL1R-IL6R and strong antioxidant role of Nigella-sativa in experimental rats.

Maiti, Smarajit; Banerjee, Amrita; Nazmeen, Aarifa; Kanwar, Mehak; Das, Shilpa

The recent outbreak of SARS CoV-2 has changed the global scenario of human lives/economy. A significant number of the non-survivors showed cardiac-renal-vasculature dysfunction. A 'cytokine storm' namely, interleukin IL6-IL1 receptors i.e. IL6R-IL1R over-functioning was reported. Here, nigellidine, an indazole-alkaloid and key-component of Nigella Sativa L. (NS) commonly known as black-cumin-seed was analyzed for COVID-19 protein-targeting and IL1R-IL6R inhibition through molecular-docking-study and biochemical-study in experimental-rat to evaluate antioxidative-capacity. The NMR/X-ray-crystallographic/Electron-microscopic structures of COVID-19 Main-protease (6LU7)/Spike-glycoprotein(6vsb)/NSP2(QHD43415_2)/Nucleocapsid(QHD43423), Human IL1R(1itb)-IL6R(1pm9) from PDB were retrieved-analyzed for receptor-ligand interaction. Then those structures were docked with nigellidine using Autodock and Patchdock-server. A brief comparison was made with nigellicine-thymoquinone from N. sativa. Where nigellidine showed highest binding-energy of -6.6 (kcal/mol), ligand-efficiency of -0.3 with COVID19 Nsp2 forming bonds with amino acid CYS240 present in binding-pocket. Nigellidine showed strong interaction with main-protease (BE:-6.38/LE:-0.29). Nigellidine showed affinity to IL1R (-6.23). The NS treated rat showed marked decline in ALP-SGPT-SGOT-malondialdehyde(MDA) than the basal-levels. From the Western-blot and activity-analysis it was observed that Nigellidine (sulfuryl-group-drug) showed no impact on Phenol-catalyzing ASTIV and Steroid-catalyzing estrogen-sulfotransferase expressions and activities in liver-tissue and thus has no influence in sulfation-mediated adverse metabolic-processes. Conclusively, nigellidine has hepato-reno-protective/antioxidant-immunomodulatory/anti-inflammatory activities with inhibit-potentials of COVID-19 proteins. Further validation is necessary.