ArticleBiophysical journal2025
Enzyme kinetics model for the coronavirus main protease including dimerization and ligand binding.
Article in Biophysical journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
6 citing papers in PubMed.
- Multiple data set Bayesian analysis synergistically boosts ITC parameter precision.Biophysical journal · 2026Article
- Linking biochemical and cellular efficacy of MERS coronavirus main protease inhibitors.ACS pharmacology & translational science · 2026Article
- SARS-CoV-2 3CL protease interaction with host factors - identifying novel drug targets.Archives of virology · 2026Review
- Linking biochemical and cellular efficacy of MERS coronavirus main protease inhibitors.bioRxiv : the preprint server for biology · 2026Article
- A Computational Community Blind Challenge on Pan-Coronavirus Drug Discovery Data.Journal of chemical information and modeling · 2026Article
- How many crystal structures do you need to trust your docking results?bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
- Update of
Authors and funding
3 authors.
Funding
Abstract
The coronavirus main protease (MPro) plays a pivotal role in viral replication and is the target of multiple antiviral drug discovery campaigns against SARS-CoV-2. In some species, CRCs of MPro enzymatic activity can exhibit biphasic behavior in which low ligand concentrations activate the enzyme, whereas higher ones inhibit it. While this behavior has been attributed to ligand-induced dimerization, quantitative enzyme kinetics models have not been fit to it. Here, we develop a kinetic model integrating dimerization and ligand binding. We perform a Bayesian regression to globally fit the model to multiple types of biochemical and biophysical data. The reversible covalent inhibitor GC376 strongly induces dimerization and binds to the dimer with positive cooperativity. In contrast, the fluorescent peptide substrate has a minor effect on dimerization but binds to the dimer with negative cooperativity. The biphasic concentration response curve occurs because, compared with substrate, the inhibitor accelerates turnover in the opposite catalytic site.
Indexed as
Identifiers
What OpenQuestion holds
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.