ArticleScience advances2025
Exploration of structure-activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment linking and active learning.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Article
- X-ray Crystallography-Guided Design and Synthesis of Cyclopentyl Heteroaryl Carboxylic Acid-Based Inhibitors of the SARS-CoV-2 Nsp3 Macrodomain (Mac1).Journal of medicinal chemistry · 2026Article
- Discovery of non-nucleoside inhibitors of the enterovirus D68 3D polymerase through crystallographic fragment and high-throughput biochemical screening.bioRxiv : the preprint server for biology · 2026Article
- Emergence of specific binding and catalysis from a designed generalist binding protein.Nature chemistry · 2026Article
- Structure, function, regulation, evolution, and therapeutic implications of PARP14.Genes & development · 2026Review
- CACHE Challenge #3: Targeting the Nsp3 Macrodomain of SARS-CoV-2.Journal of chemical information and modeling · 2026Article
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- Discovery of AVI-6451, a Potent and Selective Inhibitor of the SARS-CoV-2 ADP-Ribosylhydrolase Mac1 with Oral Efficacy In Vivo.Journal of medicinal chemistry · 2026Article
- Large scale prospective evaluation of co-folding across 557 Mac1-ligand complexes and three virtual screens.bioRxiv : the preprint server for biology · 2025Article
- Crystallographic Ensembles Reveal the Structural Basis of Binding Entropy in SARS-CoV2 Macrodomain.bioRxiv : the preprint server for biology · 2025Article
- Structure-Based Rational Design of a Selective Hydrolase Inhibitor of the Severe Acute Respiratory Syndrome Coronavirus-2 Nsp3 Macrodomain.Chembiochem : a European journal of chemical biology · 2025Article
- Article
- Discovery of AVI-6451, a Potent and Selective Inhibitor of the SARS-CoV-2 ADP-Ribosylhydrolase Mac1 with Oral Efficacy in vivo.bioRxiv : the preprint server for biology · 2025Article
- Enhanced Thompson sampling by roulette wheel selection for screening ultralarge combinatorial libraries.Journal of cheminformatics · 2025Article
- The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.bioRxiv : the preprint server for biology · 2025Article
- How many crystal structures do you need to trust your docking results?bioRxiv : the preprint server for biology · 2025Article
- Structure-based discovery of inhibitors of Mac1 domain of nonstructural protein-3 of SARS-CoV-2 by machine learning-augmented screening of chemical space.bioRxiv : the preprint server for biology · 2025Article
- Article
- Expanding Automated Multiconformer Ligand Modeling to Macrocycles and Fragments.bioRxiv : the preprint server for biology · 2025Article
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19 authors.
Funding
Abstract
The macrodomain of severe acute respiratory syndrome coronavirus 2 nonstructural protein 3 is required for viral pathogenesis and is an emerging antiviral target. We previously performed an x-ray crystallography-based fragment screen and found submicromolar inhibitors by fragment linking. However, these compounds had poor membrane permeability and liabilities that complicated optimization. Here, we developed a shape-based virtual screening pipeline-FrankenROCS. We screened the Enamine high-throughput collection of 2.1 million compounds, selecting 39 compounds for testing, with the most potent binding with a 130 μM median inhibitory concentration (IC
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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 Socratic graph.