Structure‐Guided Repurposing of FDA‐Approved Drugs Targeting CCR2 for Immune Cell‐Mediated Neuropathic Pain

C─C chemokine receptor type 2 (CCR2) significantly contributes to the pathophysiology of neuropathic pain through its role in neuroinflammatory processes. Targeting CCR2 to prevent immune cell‐mediated neuropathic pain is, therefore, a promising approach as it can reduce inflammation and pain by preventing pro‐inflammatory cells from being recruited to the site of nerve injury. Here, we conducted a comprehensive investigation into the protein‐protein interaction (PPI) between CCR2 and other microglial receptor‐related genes using the STRING database and Cytoscape 3.10.2 software. Further, we have used a structure‐guided virtual screening approach for targeting CCR2 through FDA‐approved drugs. The top hits were selected based on their high binding affinities to CCR2. After that, using PASS analysis, molecules with biophores exhibiting favorable biological properties were selected, and interaction analysis was conducted. The selected molecules were further subjected to all‐atom molecular dynamics (MD) simulation, followed by essential dynamics studies to confirm their stability and interaction dynamics with CCR2. The study pinpointed two FDA‐approved molecules, Ergotamine and Dihydroergocristine, with high predicted binding affinities toward CCR2. These compounds were identified computationally as potential CCR2 modulators; however, experimental validation is necessary to confirm their ability to inhibit CCR2 activity and reduce neuroinflammation or neuropathic pain.