ArticleProtein & cell2010
Liberation of SARS-CoV main protease from the viral polyprotein: N-terminal autocleavage does not depend on the mature dimerization mode.
Article in Protein & cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Nirmatrelvir combined with ritonavir for preventing and treating COVID-19.The Cochrane database of systematic reviews · 2023Pooled it
- Nirmatrelvir combined with ritonavir for preventing and treating COVID-19.The Cochrane database of systematic reviews · 2022Pooled it
- Conformational Dynamics of Viral Protease Precursors in Maturation, Inhibition, and Drug-Resistance Development.Viruses · 2026Review
- Cleavage at the nsp5-nsp6 site of SARS-CoV-2 main protease intermediate precursor is faster from a monomer than a dimer form.The Journal of biological chemistry · 2026Article
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 2026Review
- Solution Domain Dynamics of Monomeric SARS-CoV‑2 Main Protease Revealed by Optimized NMR Residual Dipolar Coupling Measurements.ACS physical chemistry Au · 2026Article
- A structural roadmap for the formation of the coronavirus nsp3/nsp4 double membrane vesicle pore and its implications for polyprotein processing and replication/transcription.Journal of virology · 2025Article
- Azapeptide-Based SARS-CoV-2 Main Protease Inhibitors: Design, Synthesis, Enzyme Inhibition, Structural Determination, and Antiviral Activity.Journal of medicinal chemistry · 2025Article
- Characterization of an unusual SARS-CoV-2 main protease natural variant exhibiting resistance to nirmatrelvir and ensitrelvir.Communications biology · 2025Article
- The zymogenic form of SARS-CoV-2 main protease: A discrete target for drug discovery.The Journal of biological chemistry · 2025Article
- A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system.PLoS pathogens · 2024Article
- Article
- Amino acid T25 in the substrate-binding domain of SARS-CoV-2 nsp5 is involved in viral replication in the mouse lung.PloS one · 2024Article
- Insights into the mechanism of SARS-CoV-2 main protease autocatalytic maturation from model precursors.Communications biology · 2023Article
- A comprehensive study of SARS-CoV-2 main protease (MbioRxiv : the preprint server for biology · 2023Article
- An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition.Nature communications · 2023Article
- Unmasking the Conformational Stability and Inhibitor Binding to SARS-CoV-2 Main Protease Active Site Mutants and Miniprecursor.Journal of molecular biology · 2022Article
- NMR Observation of Sulfhydryl Signals in SARS-CoV-2 Main Protease Aids Structural Studies.Chembiochem : a European journal of chemical biology · 2022Article
- Autoprocessing and oxyanion loop reorganization upon GC373 and nirmatrelvir binding of monomeric SARS-CoV-2 main protease catalytic domain.Communications biology · 2022Article
- Modulation of the monomer-dimer equilibrium and catalytic activity of SARS-CoV-2 main protease by a transition-state analog inhibitor.Communications biology · 2022Article
Corrections and comments
- Erratum issuedHigenfeld, Rolf [corrected to Hilgenfeld, Rolf]
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The main protease (M(pro)) plays a vital role in proteolytic processing of the polyproteins in the replicative cycle of SARS coronavirus (SARS-CoV). Dimerization of this enzyme has been shown to be indispensable for trans-cleavage activity. However, the auto-processing mechanism of M(pro), i.e. its own release from the polyproteins through autocleavage, remains unclear. This study elucidates the relationship between the N-terminal autocleavage activity and the dimerization of "immature" M(pro). Three residues (Arg4, Glu290, and Arg298), which contribute to the active dimer conformation of mature M(pro), are selected for mutational analyses. Surprisingly, all three mutants still perform N-terminal autocleavage, while the dimerization of mature protease and trans-cleavage activity following auto-processing are completely inhibited by the E290R and R298E mutations and partially so by the R4E mutation. Furthermore, the mature E290R mutant can resume N-terminal autocleavage activity when mixed with the "immature" C145A/E290R double mutant whereas its trans-cleavage activity remains absent. Therefore, the N-terminal auto-processing of M(pro) appears to require only two "immature" monomers approaching one another to form an "intermediate" dimer structure and does not strictly depend on the active dimer conformation existing in mature protease. In conclusion, an auto-release model of M(pro) from the polyproteins is proposed, which will help understand the auto-processing mechanism and the difference between the autocleavage and trans-cleavage proteolytic activities of SARS-CoV M(pro).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.