Computational design of an amino-pyrazole azo dye-uranyl complex as a potential SARS-CoV-2 main protease inhibitor
Aslı Öztürk Kiraz · Molecular Physics · 2025
This study presents a comprehensive computational investigation of a previously synthesised amino-pyrazole-based azo dye (AA3a), highlighting its potential as a novel inhibitor of the SARS-CoV-2 main protease (Mpro). Building upon prior synthesis and characterisation efforts, we employ density functional theory (DFT) and molecular docking techniques to evaluate the antiviral properties of AA3a. Additionally, a novel uranyl(VI) complex derived from AA3a (AA3aU) is introduced and examined for the first time. Molecular docking simulations indicate that AA3aU possesses significantly higher binding affinity toward SARS-CoV-2 Mpro (−11.21 and −11.39 kcal/mol) relative to AA3a and several benchmark antiviral drugs, including Remdesivir. ADME and toxicity predictions suggest favourable pharmacokinetic profiles and low acute toxicity for both compounds. Collectively, these findings propose AA3a as a repurposable drug-like molecule and position AA3aU as a promising metal-containing candidate for antiviral drug development and potential applications in uranium recovery for nuclear waste management. However, the lack of experimental validation remains a limitation, and future studies will be necessary to confirm these findings in vitro and in vivo.Highlights A novel coordination complex of uranyl(VI) with azo-pyrazole ligands has been modelled using computational techniques.The geometry and bonding characteristics of the uranyl-ligand system were explored through density functional theory (DFT) methods.The strong electron-donating effects of the azo-pyrazole ligands play a significant role in enhancing the stability of the complex.Analyses of frontier molecular orbitals and charge distribution suggest potential redox activity.This study provides important insights into the coordination chemistry of uranyl(VI), which is relevant to actinide research and nuclear applications.