RESUMO
Ophthalmic disorders consist of a broad spectrum of ailments that impact the structures and functions of the eye. Due to the crucial function of the retina in the vision process, the management of eye ailments is of the utmost importance, but several unmet needs have been identified in terms of the outcome measures in clinical trials, more proven minimally invasive glaucoma surgery, and a lack of comprehensive bibliometric assessments, among others. The current evaluation seeks to fulfill several of these unmet needs via a dual approach consisting of a molecular docking analysis based on the potential of ripasudil and fasudil to inhibit Rho-associated protein kinases (ROCKs), virtual screening of ligands, and pharmacokinetic predictions, emphasizing the identification of new compounds potentially active in the management of glaucoma, and a comprehensive bibliometric analysis of the most recent publications indexed in the Web of Science evaluating the management of several of the most common eye conditions. This method resulted in the finding of ligands (i.e., ZINC000000022706 with the most elevated binding potential for ROCK1 and ZINC000034800307 in the case of ROCK2) that are not presently utilized in any therapeutic regimen but may represent a future option to be successfully applied in the therapeutic scheme of glaucoma following further comprehensive testing validations. In addition, this research also analyzed multiple papers listed in the Web of Science collection of databases via the VOSviewer application to deliver, through descriptive analysis of the results, an in-depth overview of publications contributing to the present level of comprehension in therapeutic approaches to ocular diseases in terms of scientific impact, citation analyses, most productive authors, journals, and countries, as well as collaborative networks. Based on the molecular docking study's preliminary findings, the most promising candidates must be thoroughly studied to determine their efficacy and risk profiles. Bibliometric analysis may also help researchers set targets to improve ocular disease outcomes.
RESUMO
Rheumatoid arthritis (RA) is a debilitating autoimmune disorder with an inflammatory condition targeting the joints that affects millions of patients worldwide. Several unmet needs still need to be addressed despite recent improvements in the management of RA. Although current RA therapies can diminish inflammation and alleviate symptoms, many patients remain unresponsive or experience flare-ups of their ailment. The present study aims to address these unmet needs through in silico research, with a focus on the identification of novel, potentially active molecules. Therefore, a molecular docking analysis has been conducted using AutoDockTools 1.5.7 on Janus kinase (JAK) inhibitors that are either approved for RA or in advanced phases of research. The binding affinities of these small molecules against JAK1, JAK2, and JAK3, which are target proteins implicated in the pathophysiology of RA, have been assessed. Subsequent to identifying the ligands with the highest affinity for these target proteins, a ligand-based virtual screening was performed utilizing SwissSimilarity, starting with the chemical structures of the previously identified small molecules. ZINC252492504 had the highest binding affinity (-9.0 kcal/mol) for JAK1, followed by ZINC72147089 (-8.6 kcal/mol) for JAK2, and ZINC72135158 (-8.6 kcal/mol) for JAK3. Using SwissADME, an in silico pharmacokinetic evaluation showed that oral administration of the three small molecules may be feasible. Based on the preliminary results of the present study, additional extensive research is required for the most promising candidates to be conducted so their efficacy and safety profiles can be thoroughly characterized, and they can become medium- and long-term pharmacotherapeutic solutions for the treatment of RA.
