SARS-CoV-2 main protease targeting potent fluorescent inhibitors: Repurposing thioxanthones

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.