Investigating Derivatives of Tanshinone IIA Sulfonate Sodium and Chloroxine for Their Inhibition Activities against the SARS-CoV-2 Papain-like Protease

SARS-CoV-2 has caused a global pandemic of COVID-19, posing a huge threat to public health. The SARS-CoV-2 papain-like cysteine protease (PLpro) plays a significant role in virus replication and host immune regulation, which is a promising antiviral drug target. Several potential inhibitors have been identified in vitro. However, the detailed mechanism of action and structure-activity relationship require further studies. Here, we investigated the structure-activity relationships of the series of derivatives of tanshinone IIA sulfonate sodium (TSS) and chloroxine based on biochemical analysis and molecular dynamics simulation. We found that compound