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.

ABSTRACT

Background SARS-CoV-2 claimed 5,209,104 lives, infected 260,997,910 individuals, globally. Infection is caused due to exposure or susceptibility; deaths occur due to age,comorbidity,higher-viral-load, immuno-suppression, inflammation, and multi-organ failure. Theaflavin-gallate, the major black tea component, showed previous evidence to inhibit HIV-1. Purpose As theaflavin-gallate prevents experimental rat-lung injury, the study of inhibitory effects of theaflavin-gallate was done, on SARS-CoV-2proteins and various host proteins related to some adverse effects in COVID-19 patients. Study Design Currently, some prospective phytochemical, black-tea (Camellia-sinensis) extract (BTE) was initially tested in vivo in strong oxidant-mutagen arsenic-induced model rat lung injury similar to that of COVID-19 manifestations like severe inflammation, oxidative stress, lung tissue degenerations, and apoptotic death. In silico, extensive bioinformatics and molecular docking experiments were performed on all catechin or theaflavin derivatives of C. sinensis, and finally theaflavin-3'-O-gallate (TFMG) were screened for blocking or inactivation of several proteins of SARS CoV-2 and host adversely-acting proteins or factors. Methods In vivo experiments in DNA stability (ladder, comet assay), free radicals attack (malondialdehyde; MDA, superoxide dismutase SOD, catalase gel-zymogram assay), extra cellular matrix damage (matrix metalloprotease; MMP2and9 zymogram assay) and inflammation (TNF-α, ELISA). In silico experiments- molecular docking by AutoDock-Patchdock analysis, Surface Topology Calculation by CASTp, Grid-value calculation, and Ramachandran Plot study. Results The BTE showed strong protection of lung DNA and cell-matrix by decreasing MMPs, TNF-α, and free radicals, the same factors affecting COVID-19 patients. In silico data suggest that TFMG significantly blocked the entry, exit, and amino acids at catalytic active-site of more than thirty proteins including viral (nsp1,nsp2,Mainpro,∼-9.0 kcal/mol) and host inflammatory, oxidants, apoptotic, vaso-destabilizer molecules (FAS, CD40R, BCL2, TLR2, ∼ -10 and ACE1or2 ∼ -9.0 and AT1or2∼ -7.5 kcal/mol and more). When the binding energy of TFMG ranged from -7 to -11.7 kcal/mol(average -9.0) the same for hydroxy­Chloroquine ranged (-2.5 to -7 average -4.5) and dexamethasone (-3.0 to -6.0, average -4.0 kcal/mol). Conclusions TFMG has some novel physicochemical or structural properties like (ACE values of binding to all tested proteins, -300 to -625), (for TFMG H-bond acceptor or donor 15/10, for TFDG 20/13). Their topological-polar-surface-area (264Ų and 351Ų) and travel depth/height; 17.0/9.6 Å and 15.4/11.3 Å, respectively) were more potent than other compounds. Conclusively, the efficacy of TFMG may be further verified.