Interactions between HIV protease inhibitor ritonavir and human DNA repair enzyme ALKBH2: a molecular dynamics simulation study.
Unnikrishnan Paruthiyezhath ShajiNikhil TutiSusmita DasRoy AnindyaMonisha MohanPublished in: Molecular diversity (2022)
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.
Keyphrases
- dna repair
- antiretroviral therapy
- dna damage
- molecular dynamics
- hiv infected
- dna damage response
- endothelial cells
- human immunodeficiency virus
- molecular dynamics simulations
- hiv positive
- hiv aids
- molecular docking
- single molecule
- circulating tumor
- hiv testing
- induced pluripotent stem cells
- cell proliferation
- transcription factor
- oxidative stress
- young adults
- gene expression
- copy number
- locally advanced
- nucleic acid