A simplified cell-based assay to identify coronavirus 3CL protease inhibitors
Resnick, S. J.; Iketani, S.; Hong, S. J.; Zask, A.; Liu, H.; Kim, S.; Melore, S.; Nair, M. S.; Huang, Y.; Tay, N. E. S.; Rovis, T.; Yang, H. W.; Stockwell, B. R.; Ho, D. D.; Chavez, A.
Show abstract
We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the one from SARS-CoV-2, we are able to quickly identify compounds with broad or narrow spectra of activity. We further demonstrate the utility of our approach by performing a curated compound screen along with structure-activity profiling of a series of small molecules to identify compounds with antiviral activity. Throughout these studies, we observed concordance between data emerging from this assay and from live virus assays. By democratizing the testing of 3CL inhibitors to enable screening in the majority of laboratories rather than the few with extensive biosafety infrastructure, we hope to expedite the search for coronavirus 3CL protease inhibitors, to address the current epidemic and future ones that will inevitably arise.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Discovery of First-in-Class PROTAC Degraders of SARS-CoV-2 Main Protease 98%
- Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 that Exhibits Antiviral Efficacy in SARS-CoV-2 Infected African Green Monkeys 97%
- Development of a chemical probe to enable characterization of the casein kinase 1γ subfamily 96%
Similar papers in this journal
- Challenges for targeting SARS-CoV-2 proteases as a therapeutic strategy for COVID-19 98%
- Drug repurposing screening identified tropifexor as a SARS-CoV-2 papain-like protease inhibitor 96%
- Small-Molecule In Vitro Inhibitors of the Coronavirus Spike - ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 95%
Similar papers in this journal
- Repurposing of the RIPK1 selective benzooxazepin-4-one scaffold for the development of a type-III LIMK1/2 inhibitor 97%
- Synthesis and Characterization of ULK1/2 Kinase Inhibitors that Inhibit Autophagy and Upregulate Expression of Major Histocompatibility Complex I for the Treatment of Non-Small Cell Lung Cancer 96%
- A Novel Regioselective Approach to Cyclize Phage-Displayed Peptides in Combination with Epitope-Directed Selection to Identify a Potent Neutralizing Macrocyclic Peptide for SARS-CoV-2 95%
Similar papers in this journal
- Development of pyrazolopyrimidine based macrocyclic kinase inhibitors targeting AAK1 96%
- Sensitive quantification of fibroblast activation protein and high-throughput screening for inhibition by FDA-approved compounds 95%
- Shifting the selectivity of pyridopyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.