Identification of novel immuno-oncology compounds as VISTA-inhibitors for cancer therapy: A computational approach integrating virtual screening and molecular dynamics simulation

The landscape of cancer treatment has witnessed a paradigm shift with the emergence of immunotherapy, particularly the inhibition of immune checkpoints like programmed cell death protein 1 (PD-1) and its ligand PD-L1. While these therapies have revolutionized cancer treatment, a substantial proportion of patients still fail to respond, highlighting the need to explore alternative immune checkpoints. V-domain immunoglobulin suppressor of T cell activation (VISTA), a member of the B7 family, has orchestrated significant attention. Abundantly expressed in tumor-infiltrating lymphocytes, VISTA's role in regulating immune responses, especially in breast cancer, hints at its potential as a linchpin in breast cancer immunotherapy. This research focuses on molecular docking simulations of a diverse array of immuno-oncology compounds to identify potential VISTA inhibitors. Three promising candidates (Compound_6784, Compound_14718, and Compound_34839) exhibited favorable binding affinities with VISTA, forming key interactions with critical amino acid residues. ADME-Tox profiling revealed these compounds to be highly druggable, displaying minimal toxicity risks, making them suitable for clinical trials and drug development. Additionally, molecular dynamics simulations provided insights into the structural dynamics of these compounds. The metrics underline the superior stability of Compound_14718, making it the most promising candidate for further research and drug development. This research lays a robust foundation for the development of novel immunotherapies targeting VISTA in cancer treatment. The identified compounds present promising candidates for further investigation and drug development, offering hope for improved cancer immunotherapy strategies.