ArticleProceedings of the National Academy of Sciences of the United States of America2023
SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed, 60 citations in OpenAlex.
- Development of GS-441524 derivatives as potent SARS-CoV-2 Mac1 inhibitors via a direct-to-biology approach.European journal of medicinal chemistry · 2026Article
- Review
- Cellular engagement of the SARS-CoV-2 macrodomain by GS-441524 and enhancedRSC chemical biology · 2026Article
- Design, structure-based optimization and antiviral evaluation of potent inhibitors for the macrodomain Mac1 of SARS-CoV-2.Nature communications · 2026Article
- Development of GS-441524 Derivatives as Potent SARS-CoV-2 Mac1 Inhibitors via a Direct-to-Biology Approach.bioRxiv : the preprint server for biology · 2026Article
- Structure, function, regulation, evolution, and therapeutic implications of PARP14.Genes & development · 2026Review
- NADThe Journal of general virology · 2026Review
- Interactomics of SARS-CoV-2 Macrodomain 1 Reveals Putative Clients of ADP-Ribosyl Hydrolase Activity.Viruses · 2026Article
- SARS-CoV-2 nonstructural protein 3 remodels the phosphorylation of target proteins via protein-protein interactions.Microbiology spectrum · 2026Article
- Screening assay to monitor mono-ADP-ribosylhydrolase activity of viral macrodomains in cells.Communications biology · 2026Article
- CACHE Challenge #3: Targeting the Nsp3 Macrodomain of SARS-CoV-2.Journal of chemical information and modeling · 2026Article
- A murine coronavirus infection platform identifies proviral and proinflammatory activities of SARS-CoV-2 accessory protein 7a.Journal of virology · 2026Article
- 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
- Rewriting the viral script: post-translational modifications orchestrating SARS-CoV-2 pathogenesis and immune evasion.Frontiers in microbiology · 2026Review
- 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
- Interactomics of SARS-CoV-2 Macrodomain 1 Reveals Putative Clients of ADP-ribosyl Hydrolase Activity.bioRxiv : the preprint server for biology · 2025Article
- 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
- Article
- Macrodomain ADP-ribose binding but not ADP-ribosylhydrolase activity is critical for chikungunya virus infection ofbioRxiv : the preprint server for biology · 2025Article
Corrections and comments
- Update of
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Several coronavirus (CoV) encoded proteins are being evaluated as targets for antiviral therapies for COVID-19. Included in these drug targets is the conserved macrodomain, or Mac1, an ADP-ribosylhydrolase and ADP-ribose binding protein encoded as a small domain at the N terminus of nonstructural protein 3. Utilizing point mutant recombinant viruses, Mac1 was shown to be critical for both murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV virulence. However, as a potential drug target, it is imperative to understand how a complete Mac1 deletion impacts the replication and pathogenesis of different CoVs. To this end, we created recombinant bacterial artificial chromosomes (BACs) containing complete Mac1 deletions (ΔMac1) in MHV, MERS-CoV, and SARS-CoV-2. While we were unable to recover infectious virus from MHV or MERS-CoV ΔMac1 BACs, SARS-CoV-2 ΔMac1 was readily recovered from BAC transfection, indicating a stark difference in the requirement for Mac1 between different CoVs. Furthermore, SARS-CoV-2 ΔMac1 replicated at or near wild-type levels in multiple cell lines susceptible to infection. However, in a mouse model of severe infection, ΔMac1 was quickly cleared causing minimal pathology without any morbidity. ΔMac1 SARS-CoV-2 induced increased levels of interferon (IFN) and IFN-stimulated gene expression in cell culture and mice, indicating that Mac1 blocks IFN responses which may contribute to its attenuation. ΔMac1 infection also led to a stark reduction in inflammatory monocytes and neutrophils. These results demonstrate that Mac1 only minimally impacts SARS-CoV-2 replication, unlike MHV and MERS-CoV, but is required for SARS-CoV-2 pathogenesis and is a unique antiviral drug target.
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.