In-silico study of potential antiviral drug compounds against EGFR kinase domain to target non-small cell lung cancer (NSCLC)

Abstract

Purpose of Research: Worldwide, lung cancer is the biggest cause of cancer-related deaths. Cancer of non-small lung cells (NSCLC) is the most prevalent kind of lung cancer. Targeting NSCLC, we investigate the anticancer effect of antiviral drug compounds against the EGFR kinase domain. Scope of The Experiments: The 3D protein structure of the EGFR kinase domain (1XKK) was derived from the RCSB PDB library. First, an ADME study was conducted, followed by Lipinski's rule of five-based toxicity analysis of the compounds. After screening for ADME and toxicity, the remaining drugs were docked to the EGFR kinase domain (PDB ID: 1XKK). For docking, the Autodock Vina application was deployed. Using the application Discovery Studio 2019, the docking discovery was investigated. Results: The binding affinity of the standard drug compounds Afatinib Dimaleate, and Gemcitabine to the active site of the EGFR kinase domain was -8.9, and -8.4, respectively. In contrast, the binding affinity of our lead drug compound (Diphyllin) to the active region of the EGFR kinase domain was -10 kcal/mol, which is superior to the both selected standard drug compounds. In addition, the found chemical generates a greater number of hydrogen bonds than our chosen benchmark compounds, indicating that it is more stable. An examination of root means square fluctuation was done to appreciate the dynamic motions of the ligand-protein complex. Findings and Conclusions: Due to its capacity to suppress the activity of the target protein EGFR kinase domain, which plays a vital role in the progression of NSCLC, Diphyllin shows great potential as an anti-NSCLC medication. To validate further our promising findings based on preliminary and in-silico analysis, in-vitro and in-vivo investigations are necessary.