Exploring Marine Compounds for Inhibition of the BRAF V600E Mutation in Lung Cancer: A High Throughput Virtual Screening Approach

The BRAF V600E mutation is present in a variety of cancer cell types, including lung cancer, which is a leading cause of cancer-related death globally. Drugs like Dabrafenib and Vermaifenib were specifically used in targeted therapy for patients with BRAF V600E mutation. Drug resistance is typical, though, and more study is required to improve therapeutic strategies for this subset of lung cancer. Recently, marine natural compounds have emerged as a resource for the development of novel cancer therapeutics. In this study, we used virtual screening of marine compounds to find potential therapeutic candidates for NSCLC patients with the BRAF V600E mutation. We developed a receptor-based pharmacophore model and screened a library of 31,561 compounds from the Comprehensive Marine Natural Products Database (CMNPD) using a virtual screening protocol that was constructed and validated. Molecular docking was performed using CDOCKER to investigate potential inhibitors and ADMET for their toxicity and other properties. Seven compounds exhibited higher efficacy than the experimentally verified compound of BRAF mutation. A molecular dynamics simulation was performed to confirm the stability of the docked compounds and compare them with the experimentally verified compound. Our study identified, out of seven, the CMNPD7700 compound as a potential drug candidate for further development due to its high, effectiveness and molecular stability.