In silico evidence for prednisone and progesterone efficacy in recurrent implantation failure treatment

摘要

Increased expression and activation of tumor necrosis factor-alpha (TNF-alpha) could lead to recurrent implantation failure (RIF). Therefore, TNF-alpha inhibition may be a strategic way to enhance the implantation rate in women with RIF. Nowadays, monoclonal antibodies are considered an effective therapeutic method for TNF-alpha inhibition. Unfortunately, monoclonal antibody treatments have several disadvantages. Thus, the design of small molecules capable of inhibiting TNF-alpha has become critical in recent years. In silico drug repurposing of FDA-approved drugs for TNF-alpha inhibition was used in this study. PyRx tools were employed for virtual screening. Additionally, the free energy of binding, the number of hydrogen bonds, and the number of drug contacts with the protein were calculated using the molecular dynamics (MD) simulation method. Virtual screening results reveal that 17 of 2471 FDA-approved drugs benefited from favorable binding energy with TNF-alpha (delta G < -10 kcal/mol). Two of the 17 drugs, progesterone and pred- nisone, were the most frequently used without adverse effects during pregnancy. As a result, MD simulation was used to investigate these two drugs further. According to the MD simulation results, prednisone appears to have a higher affinity for TNF-alpha than progesterone, and consequently, the prednisone complex stability is higher. For the first time, this study examined the possible role of prednisone and progesterone in inhibiting TNF-alpha using in silico methods.