Related Experiment Video
Updated: Jul 24, 2026
A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
Published on: January 9, 2019
SARS-CoV-2 main protease targeting potent fluorescent inhibitors: Repurposing thioxanthones
Gönül S Batibay1, Eyüp Metin1,2
1Department of Chemistry, Faculty of Arts and Sciences, Yıldız Technical University, İstanbul, Turkiye.
Abstract:
The coronavirus disease, COVID-19, is the major focus of the whole world due to insufficient treatment options. It has spread all around the world and is responsible for the death of numerous human beings. The future consequences for the disease survivors are still unknown. Hence, all contributions to understand the disease and effectively inhibit the effects of the disease have great importance. In this study, different thioxanthone based molecules, which are known to be fluorescent compounds, were selectively chosen to study if they can inhibit the main protease of SARS-CoV-2 using various computational tools. All candidate ligands were optimized, molecular docking and adsorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were conducted and subsequently, some were subjected to 100 ns molecular dynamics simulations in conjunction with the known antiviral drugs, favipiravir, and hydroxychloroquine. It was found that different functional groups containing thioxanthone based molecules are capable of different intermolecular interactions. Even though most of the studied ligands showed stable interactions with the main protease, para-oxygen-di-acetic acid functional group containing thioxanthone was found to be a more effective inhibitor due to the higher number of intermolecular interactions and higher stability during the simulations.
Insights
Researchers explored thioxanthone molecules as potential inhibitors for the SARS-CoV-2 main protease. A specific thioxanthone derivative with a para-oxygen-di-acetic acid group showed the most promising inhibitory effects and stability.
Area of Science:
- Medicinal Chemistry
- Computational Biology
- Drug Discovery
Background:
- The global impact of coronavirus disease (COVID-19) necessitates urgent development of effective treatments.
- Understanding SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) mechanisms and identifying therapeutic targets are crucial.
Purpose of the Study:
- To investigate the potential of thioxanthone-based molecules as inhibitors of the SARS-CoV-2 main protease.
- To evaluate the binding affinity and stability of candidate molecules using computational methods.
Main Methods:
- Computational screening of diverse thioxanthone derivatives.
- Molecular docking and adsorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses.
- Molecular dynamics simulations of promising candidates against the SARS-CoV-2 main protease.
Main Results:
- Thioxanthone molecules exhibited varying degrees of intermolecular interactions with the SARS-CoV-2 main protease.
- A thioxanthone derivative featuring a para-oxygen-di-acetic acid functional group demonstrated superior inhibitory potential.
- This lead compound exhibited enhanced stability and a higher number of intermolecular interactions during molecular dynamics simulations.
Conclusions:
- Thioxanthone-based compounds represent a promising class of molecules for targeting the SARS-CoV-2 main protease.
- The para-oxygen-di-acetic acid functionalized thioxanthone is a strong candidate for further development as an antiviral agent against COVID-19.
