3C-like protease
ExPASy NiceZyme view | | ||||||||
KEGG | KEGG entry | ||||||||
---|---|---|---|---|---|---|---|---|---|
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
|
Peptidase C30, Coronavirus endopeptidase | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | Peptidase_C30 | ||||||||
SCOP2 | d1q2wb1 / SCOPe / SUPFAM | ||||||||
|
The 3C-like protease (3CLpro) or main protease (Mpro), formally known as C30 endopeptidase or 3-chymotrypsin-like protease,
The
Function
The 3C-like protease is able to
TSAVLQ-SGFRK-NH2 and SGVTFQ-GKFKK are the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase
The protease is important in the processing of the coronavirus
Position | Substrate preference |
---|---|
P5 | No strong preference |
P4 | Small hydrophobic residues
|
P3 | Positively charged residue |
P2 | High hydrophobicity and absence of beta-branch |
P1 | Glutamine |
P1' | Small residues |
P2' | Small residues |
P3' | No strong preference |
Nomenclature
Alternative names provided by the EC include 3CLpro, 3C-like protease, coronavirus 3C-like protease, Mpro, SARS 3C-like protease, SARS coronavirus 3CL protease, SARS coronavirus main peptidase, SARS coronavirus main protease, SARS-CoV 3CLpro enzyme, SARS-CoV main protease, SARS-CoV Mpro and severe acute respiratory syndrome coronavirus main protease.
As a treatment target
The protease 3CLpro is used as a
A number of
After clinical trials, in December 2021, the oral medication
The 3C-like protease inhibitor ensitrelvir received authorization to treat COVID-19 in Japan in 2022.[27][28]
In 2022, an ultralarge virtual screening campaign of 235 million molecules was able to identify a novel broad-spectrum inhibitor targeting the main protease of several coronaviruses. It is unusually not a peptidomimetic.[29]
Other 3C(-like) proteases
3C-like proteases (3C(L)pro) are widely found in
- This entry is the coronavirus 3CLpro.
- Picornaviridae have a picornavirus 3Cpro (EC 3.4.22.28; InterPro: IPR000199; MEROPS C03). This is the earliest-studied family. Examples include the ones found in poliovirus and in rhinovirus (both are members of genus Enterovirus).
- Norwalk virus.
Additional members are known from Potyviridae and non-Coronaviridae Nidovirales.[31]
See also
- 3CLpro-1
- Carmofur
- COVID Moonshot
- Ebselen
- EDP-235
- GC376
- GRL-0617
- Nirmatrelvir
- Olgotrelvir
- RAY1216
- Rupintrivir
- SIM0417
- Theaflavin digallate
- Tollovir
- Y180
- Tetrahydrocannabutol
References
- ^ PMID 32321856.
- PMID 34502033.
- PMID 17605471.
- ^ PMID 14561748.
- PMID 18845442.
- PMID 25720466.
See section: Virion Structure.
- PMID 20167482.
- PMID 22073294.
- PMID 34029993.
- ^ "Pfizer begins dosing in Phase II/III trial of antiviral drug for Covid-19". Clinical Trials Arena. 2 September 2021.
- PMID 25039866.
- S2CID 220304661.
- PMID 1738140.
- PMID 12746549.
- PMID 31312413.
- PMID 26149721.
- PMID 32045235.
- PMID 32198291.
- PMID 33556871.
- PMID 32022370.
- PMID 32226821.
- PMID 21936817.
- ^ "First-In-Human Study To Evaluate Safety, Tolerability, And Pharmacokinetics Following Single Ascending And Multiple Ascending Doses of PF-07304814 In Hospitalized Participants With COVID-19". Clinical Trials. 24 June 2021. Retrieved 3 July 2021.
- ^ Fact sheet for healthcare providers: Emergency Use Authorization for Paxlovid (PDF) (Technical report). Pfizer. 22 December 2021. LAB-1492-0.8. Archived from the original on 23 December 2021.
- ^ "Pfizer Receives U.S. FDA Emergency Use Authorization for Novel COVID-19 Oral Antiviral Treatment" (Press release). Pfizer. 22 December 2021. Archived from the original on 22 December 2021. Retrieved 22 December 2021 – via Business Wire.
- ^ "FDA Approves First Oral Antiviral for Treatment of COVID-19 in Adults". U.S. Food and Drug Administration (FDA) (Press release). 26 May 2023. Retrieved 26 May 2023. This article incorporates text from this source, which is in the public domain.
- ^ "Xocova (Ensitrelvir Fumaric Acid) Tablets 125mg Approved in Japan for the Treatment of SARS-CoV-2 Infection, under the Emergency Regulatory Approval System". Shionogi (Press release). 22 November 2022. Retrieved 28 November 2022.
- ^ Lenharo, Mariana (18 October 2023). "New Pill Helps COVID Smell and Taste Loss Fade Quickly". Scientific American. Retrieved 28 October 2023.
- PMID 35142215.
- PMID 22915796.
- PMID 12502857.
Further reading
- Chuck CP, Chow HF, Wan DC, Wong KB (2 November 2011). "Profiling of substrate specificities of 3C-like proteases from group 1, 2a, 2b, and 3 coronaviruses". PLOS ONE. 6 (11): e27228. PMID 22073294.
External links
- SARS+coronavirus+main+proteinase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Peptidase C30/C16 in coronavirus, InterPro: IPR013016. The MEROPS C16 one is the "papain-like" PL-PRO.