CE-5 blocks MERS-CoV 3CLpro activity with EC50 value of ∼12.5 μM. It inhibited SARS 3CLpro activity with IC50 value of 30nM and exhibited antiviral effect with EC50 value of 6.9μM.

Saquinavir mesylate is an HIV Protease inhibitor used in antiretroviral therapy. Saquinavir could inhibit SARS-CoV-2 3CLpro main protease.

Hesperetin is a flavanone extracted from the peel of citrus that exhibits inhibition of PDE4 and UGT. Hesperetin has antioxidative and anti-inflammatory effects as well. Hesperetin dose-dependently inhibited cleavage activity of the 3CLpro with IC50 value of 8.3μM in the cell-based assay.

Rhoifolin, a natural product isolated and purified from the leaves of Turpinia arguya Seem, hows monolithic proliferation inhibitory activities against Hela, A549 and MCF-7 cell lines, and may be beneficial for diabetic complications through their enhanced adiponectin secretion, tyrosine phosphorylation of insulin receptor-β and GLUT4. It was found to efficiently block the enzymatic activity of SARS-CoV 3CLpro.

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.

CCF0058981 is a ML300-derived, non-covalent SARS-CoV‑2 3CLpro inhibitor.

Saquinavir is an HIV Protease inhibitor used in antiretroviral therapy. Saquinavir could inhibit SARS-CoV-2 3CLpro main protease.

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

Herbacetin, a natural product isolated and purified from the herbs of Equisetum hyemale L. It was found to efficiently block the enzymatic activity of SARS-CoV 3CLpro.

PF-07321332 is an orally active 3CL protease inhibitor, binding covalently and directly to the catalytic cysteine (Cys145) residue of the enzyme. It works as an anti-SARS-CoV-2 drug.

Aloe-emodin, a natural product isolated and purified from the root of Rheum palmatum L. with a specific in vitro and in vivo anti-neuroectodermal tumor activity, reduces the toxicity and ROS induced by both monomeric and oligomeric Aβ species, appears to have some protective effect not only against hepatocyte death but also on the inflammatory response subsequent to lipid peroxidation and has a strong non-carcinogenic stimulant-laxative action when applied to the skin, although it may increase the carcinogenicity of some kind of radiation. Aloe-Emodine dose-dependently inhibited cleavage activity of the 3CLpro with IC50 value of 366μM in the cell-based assay.

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.

Amentoflavone is an inhibitor of human UDP-glucuronosyltransferases with anti-inflammatory, antioxidative, and neuroprotective effects and it can be isolated from the seeds of Ginkgo biloba L. Amentoflavone inhibited SARS-CoV 3CL(pro) with IC50 value of 8.3μM.

Disulfiram is a specific inhibitor of aldehyde-dehydrogenase (ALDH1), used for the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Disulfiram acts as an allosteric inhibitor of MERS-CoV PLpro but as a competitive (or mixed) inhibitor of SARS-CoV PLpro. It also inhibits pyroptosis by blocking gasdermin D pore formation.

16-(S)-ML188 is a non-covalent SARS-CoV 3CLpro inhibitor with good enzyme and antiviral inhibitory activity.

Dieckol exhibited SARS-CoV 3CL(pro) trans/cis-cleavage inhibitory effects with IC50 values of 2.7 and 68.1 μM, respectively. It formed extremely strong hydrogen bonds to the catalytic dyad (Cys145 and His41) of the SARS-CoV 3CL(pro).

Theaflavin-3,3'-digallate is a tea extract. Theaflavin-3,3'-digallate inhibited 3CLpro with IC50 value of 9.5μM in a fluorogenic substrate peptide assay.

16-(R)-ML188 is a non-covalent SARS-CoV 3CLpro inhibitor with good enzyme and antiviral inhibitory activity.

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.