NICEdrug.ch

NICEdrug.ch enables large-scale computational analysis of drug biochemistry, including metabolic precursors and prodrugs, their metabolic fate and degradation, enzymatic targets, and toxicity across human, Plasmodium, and E. coli metabolism.

Key Features:

• Extensive Database: Contains a collection of 250,000 bioactive molecules for systematic biochemical analysis.
• Unique Fingerprinting System: Identifies reactive similarities between drug–drug and drug–metabolite pairs to predict interactions and reactivity.
• Validation and Performance: Validated against golden standard datasets describing drugs and metabolites that share reactivity, drug toxicities, and drug targets.
• Inhibition and Toxicity Evaluation: Performs computational evaluation of inhibition and toxicity profiles of compounds, exemplified by analyses of 5-fluorouracil and proposed mitigation strategies.
• Target Identification for Disease Treatment: Proposes biochemical targets such as shikimate 3-phosphate for liver-stage malaria and suggests over 1,300 candidate drugs and food molecules to inhibit COVID-19 with insights into their inhibitory mechanisms.

Scientific Applications:

• Systematic Reactivity Identification: Enables systematic identification of small-molecule reactivity with druggable enzymes.
• Drug Repurposing Discovery: Facilitates identification of new therapeutic uses for existing bioactive molecules.
• Toxicity Prediction: Predicts toxicological profiles to inform safer drug design.
• Target Prioritization for Infectious Diseases: Supports identification and prioritization of biochemical targets and candidate inhibitors for pathogens including Plasmodium and SARS-CoV-2 (COVID-19).

Methodology:

Computational analysis of enzymatic metabolic targets, metabolic fate, and toxicity of bioactive molecules; data integration combining human, Plasmodium, and E. coli metabolism; reactivity analysis using the unique fingerprint system to analyze and predict reactivities between drugs and metabolites; validation against golden standard datasets describing shared reactivity, toxicities, and targets.