  Opioid use disorder (OUD) is a chronic and relapsing condition that involves
the continued and compulsive use of opioids despite harmful consequences. The
development of medications with improved efficacy and safety profiles for OUD
treatment is urgently needed. Drug repurposing is a promising option for drug
discovery due to its reduced cost and expedited approval procedures.
Computational approaches based on machine learning enable the rapid screening
of DrugBank compounds, identifying those with the potential to be repurposed
for OUD treatment. We collected inhibitor data for four major opioid receptors
and used advanced machine learning predictors of binding affinity that fuse the
gradient boosting decision tree algorithm with two natural language processing
(NLP)-based molecular fingerprints and one traditional 2D fingerprint. Using
these predictors, we systematically analyzed the binding affinities of DrugBank
compounds on four opioid receptors. Based on our machine learning predictions,
we were able to discriminate DrugBank compounds with various binding affinity
thresholds and selectivities for different receptors. The prediction results
were further analyzed for ADMET (absorption, distribution, metabolism,
excretion, and toxicity), which provided guidance on repurposing DrugBank
compounds for the inhibition of selected opioid receptors. The pharmacological
effects of these compounds for OUD treatment need to be tested in further
experimental studies and clinical trials. Our machine learning studies provide
a valuable platform for drug discovery in the context of OUD treatment.
