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.
3C and 3CL Protease Inhibitors |
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Cat. No. | Product Name / Activity |
7755 | Asunaprevir |
Inhibits SARS-CoV-2 Mpro activity; also inhibits hepatitis C virus NS3 protease | |
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 | |
7705 | Masitinib |
SARS-CoV-2 Mpro inhibitor | |
1748 | MG 132 |
SARS-CoV-2 Mpro inhibitor | |
7228 | Mpro 13b-K |
Coronavirus Mpro inhibitor | |
7695 | Mpro 61 |
Potent non-covalent inhibitor of SARS-CoV-2 main protease | |
7230 | MPro N3 |
Coronavirus Mpro inhibitor | |
1125 | Quercetin |
Inhibits SARS-CoV Mpro; also non-selective PI 3-kinase inhibitor | |
Degraders |
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Cat. No. | Product Name / Activity |
8802 | MPD 2 New |
SARS-CoV-2 Mpro Degrader (PROTAC®) | |
Controls |
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Cat. No. | Product Name / Activity |
7853 | Mpro 13b-H |
Negative control for Mpro 13b-K (Cat. No. 7228) | |
Other |
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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.
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