Introduction: Initial explorations into the diabetes-centric drug interactions were performed. Diabetes was queried using the DrugBank database, and Telmisartan and Valsartan were identified as candidate drugs for the treatment of this disease. Their respective 3D structural files were obtained from the PubChem website. Two ligands were separately optimized using the Chimera software to prepare the drugs for further analysis. A literature review showed that miR-27a-5p had a significant role in the pathophysiology of diabetes and its expression levels were found to be higher in diabetic patients. The sequence of the said microRNA was retrieved from the web servers of miRDB and UNAFold, and the final file was prepared for docking operations. Further employment of the ViewerLite program was done to get rid of the attached water molecules to the miRNA molecule since the docking operations require the absence of additional molecules and the removal of any inappropriate bonds. The receptor, which in this case is miR-27a-5p, was prepared in Discovery Studio for docking by adding polar hydrogens-add polar option. After that, the docking of both Telmisartan and Valsartan individually with miR-27a-5p was performed through the use of AutoDock software in order to gain the output.
Methods: Initial explorations into the diabetes-centric drug interactions were performed. Diabetes was queried using the DrugBank database, and Telmisartan and Valsartan were identified as candidate drugs for the treatment of this disease. Their respective 3D structural files were obtained from the PubChem website. Two ligands were separately optimized using the Chimera software to prepare the drugs for further analysis. A literature review showed that miR-27a-5p had a significant role in the pathophysiology of diabetes and its expression levels were found to be higher in diabetic patients. The sequence of the said microRNA was retrieved from the web servers of miRDB and UNAFold, and the final file was prepared for docking operations. Further employment of the ViewerLite program was done to get rid of the attached water molecules to the miRNA molecule since the docking operations require the absence of additional molecules and the removal of any inappropriate bonds. The receptor, which in this case is miR-27a-5p, was prepared in Discovery Studio for docking by adding polar hydrogens-add polar option. After that, the docking of both Telmisartan and Valsartan individually with miR-27a-5p was performed through the use of AutoDock software in order to gain the output.
Results: Moreover, the docking simulations have shown that through an open Guanine 18, the receptor has a strong hydrogen bond with Telmisartan. In the same direction, a strong hydrogen bond was formed between the receptor and Valsartan through the same open nucleotide. Additionally, miR-27a-5p also forms one hydrogen bond and one Pi-Pi bond with Valsartan through Cytosine 10. In addition, in the case of Telmisartan, the receptor did form a phosphoanionic bond. Moreover, Telmisartan interacted through the phospho-anion bond with Guanine 9 of miR-27a-5p.
Conclusion: These results with Valsartan show that it interacts with miR-27a-5p at Cytosine 10, but the interaction with Telmisartan has an added potential of multiple bonding, conferring a higher binding affinity with the mi-RNA and hence a higher therapeutic efficacy. Thus, the medicines are also not recommended to be administered together due to possible drug interactions. Telmisartan emerges as the drug of choice for the treatment of diabetes.
Keywords: Diabetic Neuropathy (DN); Telmisartan; Valsartan; miR-27a-5p; Drug Interactions