As the global health crisis due to evolution of mutations in SARS-CoV-2 continues, it is important to develop several effective antivirals to control the disease. Targeting papain-like protease (PLpro) of SARS-CoV-2 for drug development is a promising strategy due to its dual role in promoting viral replication and dysregulating host immune responses. Here, we screened a library of compounds to find potential inhibitors of PLpro. We find aurintricarboxylic acid (ATA) inhibits PLpro with K_i and IC₅₀ values of 16 μM and 30 μM, respectively. The binding of ATA to PLpro was further characterized using isothermal titration calorimetry, differential scanning fluorimetry, dynamic light scattering and circular dichroism spectrometry. In vitro assays showed the antiviral potential of ATA with IC₅₀ of 50 μM. In vivo efficacy was studied in Syrian hamsters and the results are being discussed.