Elucidation of the molecular interactions that enable stable interaction between HIV protease inhibitor ritonavir and human DNA repair enzyme ALKBH2: a molecular dynamics simulation study

ABSTRACTThe human DNA repair enzyme AlkB homologue-2 and 3 (ALKBH2 and ALKKBH3) repairs methyl adducts from genomic DNA. Overexpression of ALKBH2 and ALKBH3 has been implicated in both tumorigenesis and chemotherapy resistance in some cancers, including glioblastoma and renal cancer rendering it a potential therapeutic target and a diagnostic marker. However, no inhibitor is available against these important DNA repair proteins. Intending to repurpose a drug as an inhibitor of ALKBH2/ALKBH3, we performed in silico evaluation of HIV protease inhibitors and identified Ritonavir as an ALKBH2-interacting molecule. Using molecular dynamics simulation, we elucidated the molecular details of Ritonavir-ALKBH2 interaction. The present work highlights that Ritonavir might be used to target the ALKBH2-mediated DNA alkylation repair.