Identification of potential SARS-CoV-2 inhibitors among well-tolerated drugs using drug repurposing and in vitro approaches.

ABSTRACT: The 3C-like protease (3CL^pro) is essential in the SARS-CoV-2 life cycle and a promising target for antiviral drug discovery, as no similar proteases exist in humans. This study aimed to identify effective SARS-CoV-2 inhibitors among FDA-approved drugs. Previous computational analysis revealed several drugs with high binding affinity to the 3CL^pro active site. In vitro enzymatic assays confirmed that ten of these drugs effectively inhibited the enzyme. To evaluate their impact on viral replication, we used non-infectious SARS-CoV-2 sub-genomic replicons in lung and intestinal cells. Amcinonide, eltrombopag, lumacaftor, candesartan, and nelfinavir inhibited replication at low micromolar concentrations. Lumacaftor showed IC50 values of 964 nM in Caco-2 cells and 458 nM i

SUBMITTER: Orucoglu B 

PROVIDER: S-EPMC12015351 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature