ArticleProceedings of the National Academy of Sciences of the United States of America2021
Postinfection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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
49 citing papers in PubMed, 79 citations in OpenAlex.
- The CCR2 inflammatory pathway is a target for improving severe disease and pulmonary inflammation in experimental COVID-19.Virulence · 2026Article
- Discovery of broad-spectrum antivirals targeting viral proteases using in silico structural modeling and cellular analysis.Antiviral research · 2025Article
- Identifying Inhibitor-SARS-CoV2-3CLMolecules (Basel, Switzerland) · 2025Article
- An automated positive selection screen in yeast provides support for boron-containing compounds as inhibitors of SARS-CoV-2 main protease.Microbiology spectrum · 2024Article
- 3-chymotrypsin-like protease in SARS-CoV-2.Bioscience reports · 2024Review
- SARS-CoV-2 Main Protease Inhibitors That Leverage Unique Interactions with the Solvent Exposed S3 Site of the Enzyme.ACS medicinal chemistry letters · 2024Article
- Effects of sEH inhibition on the eicosanoid and cytokine storms in SARS-CoV-2-infected mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Azapeptides with unique covalent warheads as SARS-CoV-2 main protease inhibitors.Antiviral research · 2024Article
- Potent small molecule inhibitors against the 3C protease of foot-and-mouth disease virus.Microbiology spectrum · 2024Article
- Article
- On the origins of SARS-CoV-2 main protease inhibitors.RSC medicinal chemistry · 2024Review
- A novel class of broad-spectrum active-site-directed 3C-like protease inhibitors with nanomolar antiviral activity against highly immune-evasive SARS-CoV-2 Omicron subvariants.Emerging microbes & infections · 2023Article
- Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review.European journal of medicinal chemistry · 2023Review
- A Systematic Survey of Reversibly Covalent Dipeptidyl Inhibitors of the SARS-CoV-2 Main Protease.Journal of medicinal chemistry · 2023Article
- Post-infection treatment with the E protein inhibitor BIT225 reduces disease severity and increases survival of K18-hACE2 transgenic mice infected with a lethal dose of SARS-CoV-2.PLoS pathogens · 2023Article
- Exploring potential SARS-CoV-2 Mpro non-covalent inhibitors through docking, pharmacophore profile matching, molecular dynamic simulation, and MM-GBSA.Journal of molecular modeling · 2023Article
- A Novel Y-Shaped, S-O-N-O-S-Bridged Cross-Link between Three Residues C22, C44, and K61 Is Frequently Observed in the SARS-CoV-2 Main Protease.ACS chemical biology · 2023Article
- Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro.ACS central science · 2023Article
- Article
- Broad-Spectrum Cyclopropane-Based Inhibitors of Coronavirus 3C-like Proteases: Biochemical, Structural, and Virological Studies.ACS pharmacology & translational science · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a serious global public health threat. The 3C-like protease (3CLpro) is a virus protease encoded by SARS-CoV-2, which is essential for virus replication. We have previously reported a series of small-molecule 3CLpro inhibitors effective for inhibiting replication of human coronaviruses including SARS-CoV-2 in cell culture and in animal models. Here we generated a series of deuterated variants of a 3CLpro inhibitor, GC376, and evaluated the antiviral effect against SARS-CoV-2. The deuterated GC376 displayed potent inhibitory activity against SARS-CoV-2 in the enzyme- and the cell-based assays. The K18-hACE2 mice develop mild to lethal infection commensurate with SARS-CoV-2 challenge doses and were proposed as a model for efficacy testing of antiviral agents. We treated lethally infected mice with a deuterated derivative of GC376. Treatment of K18-hACE2 mice at 24 h postinfection with a derivative (compound 2) resulted in increased survival of mice compared to vehicle-treated mice. Lung virus titers were decreased, and histopathological changes were ameliorated in compound 2-treated mice compared to vehicle-treated mice. Structural investigation using high-resolution crystallography illuminated binding interactions of 3CLpro of SARS-CoV-2 and SARS-CoV with deuterated variants of GC376. Taken together, deuterated GC376 variants have excellent potential as antiviral agents against SARS-CoV-2.
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.