Related Experiment Video
Updated: Sep 13, 2025
Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Supercomputing Multi-Ligand Modeling, Simulation, Wavelet Analysis and Surface Plasmon Resonance to Develop Novel
Hong Li1,2,3, Hailong Su4, Akari Komori3
1Department of Traditional Chinese Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Abstract:
Background/Objectives: Combination therapies using traditional Chinese medicine and Western drugs have gained attention for their enhanced therapeutic effects and reduced side effects. Toujie Quwen Granules (TQG), known for its antiviral properties, particularly against respiratory viruses, could offer new treatment strategies when combined with antiviral drugs like arbidol, especially for diseases such as Coronavirus disease. This study investigates the synergistic mechanisms between arbidol and components from TQG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). Methods: We identified compounds from TQG via existing data. Multi-ligand molecular docking, pharmacokinetic/toxicity screening, and preliminary simulations were performed to assess potential synergistic compounds with arbidol. UPLC-Q-Exactive Orbitrap-MS verified the presence of these compounds. Extended simulations and in vitro assays, including Luciferase and surface plasmon resonance, validated the findings. Results: Five compounds interacted with arbidol in synergy based on docking and preliminary dynamics simulation results. Only Baicalein (HQA004) could be identified in the herbal remedy by untargeted metabolomics, with ideal pharmacokinetic properties, and as a non-toxic compound. Extended simulations revealed that HQA004 enhanced arbidol's antiviral activity via a "Far" Addition Mechanism #2, with an optimal 2:1 arbidol:HQA004 ratio. The movements of arbidol (diffusion and intramolecular conformational shifts) in the system were significantly reduced by HQA004, which may be the main reason for the synergism that occurred. In vitro experiments confirmed an increased inhibition of Mpro by the combination. Conclusions: HQA004 demonstrated synergistic potential with arbidol in inhibiting Mpro. The development of combination therapies integrating Western and herbal medicine is supported by these findings for effective antiviral treatments.
