Repurposing Thiazole/Benzothiazole-Based Thiazolidinone Derivatives as SARS-CoV-2 Main Protease (Mpro) Inhibitors: An Integrated Computational and Experimental Study

Background/Objectives: SARS-CoV-2, the causative agent of COVID-19, relies on its main protease (Mpro) for viral replication, making this enzyme an attractive target for antiviral drug development. In the present study, we investigated whether a library of previously synthesized thiazole/benzothiazole-based thiazolidinone derivatives, originally developed as anti-HIV agents, could be repurposed as SARS-CoV-2 Mpro inhibitors.

Methods

A total of 85 thiazole/benzothiazole-based thiazolidinone derivatives were computationally screened against SARS-CoV-2 Mpro using molecular docking. Based on their predicted binding affinities, fifteen were selected for experimental evaluation. Enzymatic assays were used to quantify Mpro inhibition, and the compounds with the clearest enzymatic activity were then examined for their ability to limit viral replication in cell culture models challenged with the Delta and Omicron variants.