In silico analysis of RPS4X (X-linked ribosomal protein) with active components from black seed (Nigella sativa) for potential treatment of multiple sclerosis

Abstract

Multiple sclerosis is a complex disorder that is caused by demyelination and loss of axonal parts in the central nervous system. It is caused by many environmental and genetic factors. Various genetic markers such as HLA-DRB1, myelin basic protein, oligodendrocytic glycoprotein, caspase 1, interleukin-1, CD-20, Gap-43 protein, RPS4X (X-linked ribosomal protein), and fibrinogen are some of the factors involved in multiple sclerosis. The ribosomal protein S4 is upregulated in the MS brain. This disease is treated with several synthetic medicines and stem cell therapies which are associated with various side effects. Nigella sativa possesses neuroprotective, antioxidant, and anti-inflammatory properties with no potential side effects which make this plant a potential candidate for the treatment of multiple sclerosis in animal models as well as humans. However, its implications in MS are mainly limited to thymoquinone application. Thus, the present study is an attempt to investigate the role of bioactive molecules other than thymoquinone. Using Auto Dock vina, we investigated the interaction between the RPS4X gene protein of both quail and mouse with the herbal components. Although thymoquinone is the main active component of this herb, it was excluded due to its higher binding energy (-5.0 kcal/mol mouse, -5.3 kcal/mol quail) for the RPS4X gene. Out of 56 components quercetin (-7.0 kcal/mol mouse, -6.9 kcal/mol quail), and kaempferol (-6.7 kcal/mol mouse, -6.5 quail) were identified as the most potent components antioxidant based on their affinity values. Both of them have low toxicity and based on Density Functional Theory (DFT) Calculation kaempferol was the more reactive while quercetin was more stable. The molecular dynamic simulations showed stable binding interaction and flexibility of docked complexes confirming kaempferol and quercetin as potential binders for the proteins. Our data support the interaction between gene and active components of Nigella sativa and suggest their potential involvement in multiple sclerosis treatment.