Design of an inhibitory ligand based on interleukin 6 receptor for disruption and inhibition of interleukin 6-dependent inflammatory signaling pathway in Covid-19 patients

The covid 19 pandemic since it was first discovered in late 2019 has made a great impact on human health worldwide. At present, no specific drug and treatment methods have been discovered to treat this disease. On the other hand, excessive inflammation due to high cytokines secretion in Covid-19 patients results in fatal effects including organ failure and death. Therefore, to define a better understanding of the pathophysiology of this virus, scientists are trying to use a variety of methods such as examining some available anti-inflammatory drugs or evaluating Insilico inhibitory compounds as IL-6 receptor (IL-6R) inhibitors to modulate parts of the immune system.

In this study, after designing Insilico, docking was performed between inhibitory ligands and IL6R. Subsequently, the appropriated ligand was evaluated for toxicity and allergy, and ADME prediction (absorption, distribution, metabolism, and excretion).

The results of the molecular docking showed that between the non-polar parts of the designed inhibitory ligand composition, mainly with parts of IL-6R protein containing amino acids of Arg118, Thr120, ser122 hydrogen interaction took place. The amino acids of Arg118, Ser122, Trp115, Thr120, Glu96, , Pro121, Val93, Thr125 and Pro94 also demonstrate ester interactions.
Discussion and

Docking results demonstrated that out of 100 studied ligands, [03] unknown (24) has more suitable binding energy (-114.648) with the IL-6R than other ligands and this energy level indicates a favorable interaction between this inhibitory compound and IL-6R through amino acids of Ser122, Arg118, Trp115, Glu96, Thr120, Pro121, Val93, Pro94, and Thr125. Clinical studies are needed to prove the inhibitory effect of this ligand on the IL6R.