GRL0617 is a noncovalent lead inhibitor of Plpro. It inhibited SARS-CoV viral replication in Vero E6 cells with an EC50 of 15μM。

Tanshinone IIA is a naturally occuring cardioprotective agent which can inhibit NF-κB and AP-1 DNA binding and display antioxidant and anti-inflammatory properties. Tanshinone IIA showed inhibitory effect on PL(pro) with IC50 value of 1.6μM and less inhibitory effect on 3CLpro with IC50 value of 89.1μM.

Tanshinone I, an active principle isolated from the roots of Salvia miltiorrhiza (Danshen), is an inhibitor of type IIA human recombinant sPLA2 and rabbit recombinant cPLA2 with IC50s of 11 μM and 82 μM, respectively, is structurally similar to tanshinone IIA and may possess similar cytotoxic effects on tumor cells. Tanshinone I showed inhibitory effect on PL(pro) with IC50 value of 8.8μM and less inhibitory effect on 3CLpro with IC50 value of 38.7μM.

6-Mercaptopurine Monohydrate inhibits the de novo purine synthesis through incorporation of thiopurine methyltransferase metabolites into DNA and RNA, it is a widely used antileukemic agent and immunosuppressive drug. 6-mercaptopurine was found to inhibit SARS-CoV PLpro.

Dihydrotanshinone I, a natural product isolated and purified from the roots of Salvia miltiorrhiza Bge., exhibits dose-dependent inhibition towards HLM-catalyzed propofol glucuronidation. Dihydrotanshinone I showed inhibitory effect on PL(pro) with IC50 value of 4.9μM and less inhibitory effect on 3CLpro with IC50 value of 14.4μM.

Tanshinone IIA sulfonate sodium is a water-soluble derivative of tanshinone IIA, which acts as an inhibitor of store-operated Ca2+entry (SOCE), and is used to treat cardiovascular disorders.

6-Thioguanine belongs to the thiopurine family of drugs that also include mercaptopurine and azathioprine, which are examples of antimetabolites, and is a purine analogue of the nucleobase guanine. It was found to inhibit SARS-CoV PLpro. 6-Thioguanine disrupts cytosine methylation by DNA methyltransferases in vitro and acts as a DNA demethylating agent in vivo.

Rosmariquinone showed inhibitory effect on PL(pro) and 3CLpro with IC50 values of 30μM and 21.1μM, respectively.

Cryptotanshinone is a potent STAT3 inhibitor (IC50 =4.6 μM) and inhibits STAT3 Tyr705 phosphorylation in DU145 prostate cancer cells. Cryptotanshinone showed inhibitory effect on PL(pro) with IC50 value of 0.8μM and slight inhibitory effect on 3CLpro with IC50 value of 226.7μM.

Tanshinone IIB (TSB), a natural product isolated and purified from the roots of Salvia miltiorrhiza, can significantly inhibit the DNA laddering, cytotoxicity and apoptosis of rat cortical neurons induced by staurosporine in a concentration-dependent manner. Tanshinone IIB showed inhibitory effect on PL(pro) with IC50 value of 10.7μM and less inhibitory effect on 3CLpro with IC50 value of 24.8μM.

Methyl tanshinonate showed inhibitory effect on PL(pro) with IC50 value of 9.2μM and less inhibitory effect on 3CLpro with IC50 value of 21.1μM.

Hirsutenone, a natural product isolated and purified from the eaves of Alnus nepalensis, exhibits anti-cancer effect against prostate cancer through a direct physical inhibition of Akt1/2, attenuates adipogenesis by directly targeting PI3K and ERK during MCE in 3T3-L1 preadipocytes, underscoring the potential therapeutic application of Hirsutenone in preventing obesity, and may exert a preventive effect against microbial endotoxin lipopolysaccharide-induced inflammatory skin diseases through inhibition of ERK pathway-mediated NF-kappaB activation. Hirsutenone showed potent PL(pro) inhibitory activity with IC50 value of 4.1µM.