Interactions between HIV protease inhibitor ritonavir and human DNA repair enzyme ALKBH2: a molecular dynamics simulation study

The human DNA repair enzyme AlkB homologue-2 (ALKBH2) repairs methyl adducts from genomic DNA. Overexpression of ALKBH2 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, 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. [GRAPHICS] .

Automated summary

ALKBH2 is a human DNA repair enzyme that repairs methyl adducts in genomic DNA. Overexpression of ALKBH2 has been associated with tumorigenesis and chemotherapy resistance in certain cancers. In this study, we identified Ritonavir as a potential inhibitor of ALKBH2 through in silico evaluation of HIV protease inhibitors. Molecular dynamics simulation provided insights into the interaction between Ritonavir and ALKBH2. This suggests that Ritonavir could be used to target ALKBH2-mediated DNA alkylation repair.