3C and 3CL Proteases

3C and 3C-like proteases are cysteine proteases found in positive sense RNA viruses such as coronaviruses and picornaviruses. 3CLpro from beta coronaviruses is also known as main protease, Mpro. These proteases are key components of the viral life cycle and, as such, are a potential target for the development of inhibitors to treat coronavirus infection.

Literature (1)

3C and 3CL Protease Inhibitors

Cat. No. Product Name / Activity
0448 Calpeptin
SARS-CoV-2 Mpro inhibitor; also inhibits calpain and cathepsin L
0460 Cinanserin hydrochloride
SARS-CoV Mpro inhibitor; also 5-HT2 antagonist
3807 Disulfiram
SARS-CoV-2 Mpro inhibitor; also reversibly stimulates SERCA Ca2+-ATPase
5245 Ebselen
Inhibits SARS-CoV-2 Mpro in vitro; glutathione peroxidase mimic
1748 MG 132
SARS-CoV-2 Mpro inhibitor
7228 MPro 13b
Coronavirus Mpro inhibitor
7230 MPro N3
Coronavirus Mpro inhibitor
1125 Quercetin
Inhibits SARS-CoV Mpro; also non-selective PI 3-kinase inhibitor
6414 Rupintrivir
Potent and selective irreversible human rhinovirus 3Cpro inhibitor


Cat. No. Product Name / Activity
6960 ABT 199
Exhibits binding to SARS-CoV-2 Mpro in a virtual screen; selective and high affinity Bcl-2 inhibitor

3C and 3C-like proteases are cysteine proteases identified in coronaviruses and picornaviruses, such as SARS-CoV, poliovirus and rhinovirus. The active form of these proteases is dimeric, with each monomer contributing a cysteine-histidine catalytic domain to the active site. The individual monomers are inactive without dimerization. 3C and 3CL proteases are essential to the life cycle of the virus, and are key to the proteolytic processing of polyproteins that are translated from viral RNA by host cell machinery.

The vital role of 3C and 3CL proteases in viral replication, and the low sequence homology between viral proteases and host cell proteases, has resulted in them being a target of interest for the development of antivirals. Inhibition of the enzyme can be achieved by preventing dimerization of the two inactive monomers, or preventing binding of the enzymes substrate.

Coronavirus Mpro

Mpro, also known as 3CLpro, is the main protease found in beta coronaviruses, including SARS-CoV, MERS-COV and SARS-CoV-2. SARS-CoV and SARS-CoV-2 Mpro share 96% sequence homology. In the SARS-CoV-2 viral life cycle, Mpro cleaves polyproteins from the viral genome at 11 conserved sites, and mediates the majority of cleavage events required for the maturation of the virus.

The structure of Mpro is conserved across all coronaviruses, with three domains (domains I to III) and a chymotrypsin-like two-domain fold at the N-terminus. The cysteine-histidine catalytic dyad is located in a cleft between domains I and II of each monomer, while domain III is required for dimerization. Residues 1 to 7 of the N-terminus are thought to play a role in the enzyme's catalytic activity.

SARS-CoV-2 M<sup>pro</sup> protein structure

Figure 1: Structure of SARS-CoV-2 Mpro. Structure taken from Protein Data Bank, PDBID: 7BQY. Jin et al (2020) Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 582: 289-293

External sources of pharmacological information for 3C and 3CL Proteases :

    Literature for 3C and 3CL Proteases

    Tocris offers the following scientific literature for 3C and 3CL Proteases to showcase our products. We invite you to request* your copy today!

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