The Mac1 ADP-ribosylhydrolase is a therapeutic target for SARS-CoV-2
et al., eLife, doi:10.7554/elife.103484, Nov 2025
In vitro and mouse study showing antiviral benefits with AVI-4206, a novel SARS-CoV-2 Mac1 macrodomain inhibitor. Authors developed AVI-4206 through structure-based drug design, achieving ~20 nM potency against Mac1 with high selectivity over human macrodomains. The compound showed cellular target engagement via CETSA assays but limited efficacy in simple cell culture models. However, AVI-4206 demonstrated antiviral activity in more physiologically relevant systems including human airway organoids and monocyte-derived macrophages, reducing viral replication 10-100 fold. In K18-hACE2 transgenic mice infected with SARS-CoV-2, AVI-4206 treatment resulted in ~70% survival compared to 0% in vehicle controls, reduced viral loads in lungs (~100-fold at day 7) and brain, and enhanced antiviral cytokine production. Authors also demonstrated efficacy in wild-type mice with mouse-adapted SARS-CoV-2. The mechanism involves inhibiting Mac1's ADP-ribosylhydrolase activity, which normally counters interferon-induced PARP-mediated ADP-ribosylation, thereby restoring host antiviral immune responses. AVI-4206 showed favorable pharmacokinetics via intraperitoneal administration and minimal off-target effects in safety panels.
Suryawanshi et al., 19 Nov 2025, peer-reviewed, 31 authors.
Contact: melanie.ott@gladstone.ucsf.edu, adam.renslo@ucsf.edu, alan.ashworth@ucsf.edu, jfraser@fraserlab.com.
The Mac1 ADP-ribosylhydrolase is a therapeutic target for SARS-CoV-2
eLife, doi:10.7554/elife.103484
This important study presents the development of a novel inhibitor for SARS-CoV-2 Mac1 that has potential utility both as an antiviral therapeutic and as a tool for probing the molecular mechanisms by which infection-induced ADP-ribosylation triggers robust host antiviral responses. Though minor gaps in understanding the compound's precise molecular mechanism of action and its ability to target Mac1 from other coronaviruses remain, the evidence for its effects on SARS-CoV-2 in relevant biological models is compelling.
Additional information Competing interests Rahul K Suryawanshi, Priyadarshini Jaishankar, Galen J Correy, Moira M Rachman, Patrick C O'Leary, Taha Y Taha, Francisco J Zapatero-Belinchón, Morgan E Diolaiti, Mauricio Montano, Takaya Togo, Ryan L Gonciarz: listed as an inventor on a patent application (Mac1 Inhibitors and Uses Thereof U.S. Provisional Application No. 63/631,958 filed April 9, 2024) describing small molecule macrodomain inhibitors, which includes compounds described herein. Nevan J Krogan: The Krogan laboratory has received research support from Vir Biotechnology, F Hoffmann-La Roche and Rezo Therapeutics. NJK has a financially compensated consulting agreement with Maze Therapeutics. He is on the Board of Directors and is President of Rezo Therapeutics and is a shareholder in Tenaya Therapeutics, Maze Therapeutics, Rezo Therapeutics, and GEn1E Lifesciences. He is also listed as an inventor on a patent application (Mac1 Inhibitors and Uses Thereof U.S. Provisional Application No. 63/631,958 filed April 9, 2024) describing small molecule macrodomain inhibitors, which includes compounds described herein. Brian K Shoichet: co-founder of BlueDolphin LLC, Epiodyne Inc, and Deep Apple Therapeutics, Inc, and serves on the SRB of Genentech, the SAB of Schrodinger LLC, and the SAB of Vilya Therapeutics. Also listed as an inventor on a patent application (Mac1 Inhibitors and Uses Thereof
Additional files Supplementary files Supplementary file 1. X-ray data collection and..
References
Alhammad, Parthasarathy, Ghimire, Kerr, Connor et al., SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in mice, PNAS, doi:10.1073/pnas.2302083120
Bao, Deng, Huang, Gao, Liu et al., The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice, Nature, doi:10.1038/s41586-020-2312-y
Case, Rothlauf, Chen, Liu, Zhao et al., Neutralizing Antibody and Soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2, Cell Host & Microbe, doi:10.1016/j.chom.2020.06.021
Collins, Ng, Talon, Nekrosiute, Krojer et al., Gentle, fast and effective crystal soaking by acoustic dispensing, Acta Crystallographica. Section D, Structural Biology, doi:10.1107/S205979831700331X
Correy, Kneller, Phillips, Pant, Russi et al., The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and x-ray diffraction at room temperature, Science Advances, doi:10.1126/sciadv.abo5083
Correy, Rachman, Togo, Gahbauer, Doruk et al., Exploration of structure-activity relationships for the SARS-CoV-2 macrodomain from shapebased fragment linking and active learning, Science Advances, doi:10.1126/sciadv.ads7187
Dasovich, Leung, PARPs and ADP-ribosylation: Deciphering the complexity with molecular tools, Molecular Cell, doi:10.1016/j.molcel.2023.04.009
Dasovich, Zhuo, Goodman, Thomas, Mcpherson et al., Highthroughput activity assay for screening inhibitors of the SARS-CoV-2 Mac1 Macrodomain, ACS Chemical Biology, doi:10.1021/acschembio.1c00721
Dea, PARP and PARG inhibitors in cancer treatment, Genes & Development, doi:10.1101/gad.334516.119
Evans, Murshudov, How good are my data and what is the resolution?, Acta Crystallographica. Section D, Biological Crystallography, doi:10.1107/S0907444913000061
Gahbauer, Correy, Schuller, Ferla, Doruk et al., Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2, PNAS, doi:10.1073/pnas.2212931120
Grunewald, Chen, Kuny, Maejima, Lease et al., The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression, PLOS Pathogens, doi:10.1371/journal.ppat.1007756
Ivashkiv, Epigenetic regulation of macrophage polarization and function, Trends in Immunology, doi:10.1016/j.it.2012.11.001
Kabsch, XDS, Acta Crystallographica. Section D, Biological Crystallography, doi:10.1107/S0907444909047337
Kar, Chatrin, Đukić, Suyari, Schuller et al., PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation, The EMBO Journal, doi:10.1038/s44318-024-00126-0
Kasson, Dharmapriya, Kim, Selective monitoring of the protein-free ADP-ribose released by ADP-ribosylation reversal enzymes, PLOS ONE, doi:10.1371/journal.pone.0254022
Kawai, Akira, The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors, Nature Immunology, doi:10.1038/ni.1863
Kerr, Parthasarathy, Schwarting, Connor, Pfannenstiel et al., PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell-and tissue-specific manner, Journal of Virology, doi:10.1128/jvi.00885-23
Kerr, Pfannenstiel, Alhammad, Connor, Ghimire et al., Mutation of a highly conserved isoleucine residue in loop 2 of several β-Coronavirus macrodomains indicates that enhanced ADP-Ribose binding is detrimental to infection, bioRxiv, doi:10.1101/2024.01.03.574082
Khalid, Chen, Soveg, Taha, Tabata et al., Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants, bioRxiv, doi:10.1101/2024.03.05.583578
Kim, Shin, Type I and III interferon responses in SARS-CoV-2 infection, Experimental & Molecular Medicine, doi:10.1038/s12276-021-00592-0
Lee, Amick, Aschenbrenner, Barr, Benjamin et al., Discovery of Potent SARS-CoV-2 Nsp3 macrodomain inhibitors uncovers lack of translation to cellular antiviral response, bioRxiv, doi:10.1101/2024.08.19.608619
Leung, Griffin, Bosch, Fehr, The conserved macrodomain is a potential therapeutic target for coronaviruses and alphaviruses, Pathogens, doi:10.3390/pathogens11010094
Li, Hilgenfeld, Whitley, Clercq E ; A, Therapeutic strategies for COVID-19: progress and lessons learned, Nature Reviews. Drug Discovery, doi:10.1038/s41573-023-00672-y
Li, Huang, Yu, Wan, Chiu et al., Human airway and nasal organoids reveal escalating replicative fitness of SARS-CoV-2 emerging variants, PNAS, doi:10.1073/pnas.2300376120
Liebschner, Afonine, Baker, Bunkóczi, Chen et al., Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix, Acta Crystallographica. Section D, Structural Biology, doi:10.1107/S2059798319011471
Lord, Ashworth, PARP inhibitors: Synthetic lethality in the clinic, Science, doi:10.1126/science.aam7344
Martinez, Asawa, Cyr, Zakharov, Urban et al., A widely-applicable high-throughput cellular thermal shift assay (CETSA) using split Nano Luciferase, Scientific Reports, doi:10.1038/s41598-018-27834-y
Mccoy, Grosse-Kunstleve, Adams, Winn, Storoni et al., Phaser crystallographic software, Journal of Applied Crystallography, doi:10.1107/S0021889807021206
Mccracken, Justice, Wijeratne, Mosley, Inflect: Optimizing computational workflows for thermal proteome profiling data analysis, Journal of Proteome Research, doi:10.1021/acs.jproteome.0c00872
Mcpherson, Abraham, Sreekumar, Ong, Cheng et al., ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical for virus replication and virulence, PNAS, doi:10.1073/pnas.1621485114
Michalska, Kim, Jedrzejczak, Maltseva, Stols et al., Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes, IUCrJ, doi:10.1107/S2052252520009653
Minkoff, Innate immune evasion strategies of SARS-CoV-2, Nature Reviews, doi:10.1038/s41579-022-00839-1
Neufeldt, Cerikan, Frankish, Lee, Plociennikowska et al., SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB, Communications Biology, doi:10.1038/s42003-021-02983-5
O'connor, Ferraris, Fehr, An update on the current state of SARS-CoV-2 Mac1 inhibitors, Pathogens, doi:10.3390/pathogens12101221
Oladunni, Park, Pino, Gonzalez, Akhter et al., Lethality of SARS-CoV-2 infection in K18 human angiotensinconverting enzyme 2 transgenic mice, Nature Communications, doi:10.1038/s41467-020-19891-7
Papini, Ullah, Ranjan, Zhang, Wu et al., Proof-of-concept studies with a computationally designed M pro inhibitor as a synergistic combination regimen alternative to Paxlovid, PNAS, doi:10.1073/pnas.2320713121
Parthasarathy, Saenjamsai, Hao, Ferkul, Pfannenstiel et al., PARP14 is an interferon (IFN)-induced host factor that promotes IFN production and affects the replication of multiple viruses, bioRxiv, doi:10.1101/2024.04.26.591186
Pearce, Krojer, Bradley, Collins, Nowak et al., A multi-crystal method for extracting obscured crystallographic states from conventionally uninterpretable electron density, Nature Communications, doi:10.1038/ncomms15123
Platanias, Mechanisms of type-I-and type-II-interferon-mediated signalling, Nature Reviews. Immunology, doi:10.1038/nri1604
Ribeiro, Russo, Duré, Hoch, Interferon-induced ADP-ribosylation: technical developments driving ICAB discovery, Bioscience Reports, doi:10.1042/BSR20240986
Robertson, Bedard, Mcnally, Shaia, Clancy et al., Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19, Nature Communications, doi:10.1038/s41467-023-40076-5
Sachs, Papaspyropoulos, Zomer-Van Ommen, Heo, Böttinger et al., Long-term expanding human airway organoids for disease modeling, The EMBO Journal, doi:10.15252/embj.2018100300
Sanchez, Ronzetti, Owens, Antony, Voss et al., Real-time cellular thermal shift assay to monitor target engagement, ACS Chemical Biology, doi:10.1021/acschembio.2c00334
Savitski, Reinhard, Franken, Werner, Savitski et al., Tracking cancer drugs in living cells by thermal profiling of the proteome, Science, doi:10.1126/science.1255784
Schuller, Correy, Gahbauer, Fearon, Wu et al., Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking, Science Advances, doi:10.1126/sciadv.abf8711
Schuller, Zarganes-Tzitzikas, Bennett, Cesco, Fearon et al., Discovery and development strategies for SARS-CoV-2 NSP3 macrodomain inhibitors, Pathogens, doi:10.3390/pathogens12020324
Sefik, Qu, Junqueira, Inflammasome activation in infected macrophages drives COVID-19 pathology, Nature, doi:10.1038/s41586-022-04802-1
Shifrut, Carnevale, Tobin, Roth, Woo et al., Genome-wide CRISPR screens in primary human T cells reveal key regulators of immune function, Cell, doi:10.1016/j.cell.2018.10.024
Simoneau, Chen, Xing, Hayashi, Chen et al., NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2overexpressing human airway organoids, Scientific Reports, doi:10.1038/s41598-024-66003-2
Suryawanshi, Ma, Syed, Brazer, Saldhi et al., Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination, Nature, doi:10.1038/s41586-022-04865-0
Taha, Chen, Hayashi, Tabata, Walcott et al., Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6, Nature Communications, doi:10.1038/s41467-023-37787-0
Taha, Suryawanshi, Correy, Mccavitt-Malvido, Leary et al., A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo, PLOS Pathogens, doi:10.1371/journal.ppat.1011614
Tan, Zhang, Ansari, Jadhav, Tan et al., Design of a SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model, Science, doi:10.1126/science.adm9724
Von Delft, Hall, Kwong, Purcell, Saikatendu et al., Accelerating antiviral drug discovery: lessons from COVID-19, Nature Reviews. Drug Discovery, doi:10.1038/s41573-023-00692-8
Voorneveld, Rack, Ahel, Overkleeft, Van Der Marel et al., Synthetic α-and β-Ser-ADP-ribosylated Peptides Reveal α-Ser-ADPr as the Native Epimer, Organic Letters, doi:10.1021/acs.orglett.8b01742
Voth, Connor, Kerr, Doerger, Schwarting et al., Unique mutations in the murine hepatitis virus macrodomain differentially attenuate virus replication, indicating multiple roles for the macrodomain in coronavirus replication, Journal of Virology, doi:10.1128/JVI.00766-21
Wazir, Parviainen, Pfannenstiel, Duong, Cluff et al., Discovery of 2-Amide-3-methylester Thiophenes that Target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an Antiviral Target, Journal of Medicinal Chemistry, doi:10.1021/acs.jmedchem.3c02451
Xie, Muruato, Lokugamage, Narayanan, Zhang et al., An infectious cDNA clone of SARS-CoV-2, Cell Host & Microbe, doi:10.1016/j.chom.2020.04.004
Zheng, Wong, Li, Verma, Ortiz et al., COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice, Nature, doi:10.1038/s41586-020-2943-z
DOI record:
{
"DOI": "10.7554/elife.103484",
"ISSN": [
"2050-084X"
],
"URL": "http://dx.doi.org/10.7554/elife.103484",
"abstract": "<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a threat to public health. Current therapeutics remain limited to direct-acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-ribosylhydrolase macrodomain (Mac1) that plays an important role in the coronaviral life cycle by suppressing host innate immune responses. Genetic inactivation of Mac1 abrogates viral replication in vivo by potentiating host innate immune responses. However, it is unknown whether this can be achieved by pharmacologic inhibition and can therefore be exploited therapeutically. Here, we report a potent and selective lead small molecule, AVI-4206, that is effective in an in vivo model of SARS-CoV-2 infection. Standard cellular models indicate that AVI-4206 has high target engagement and can weakly inhibit viral replication in a gamma interferon- and Mac1 catalytic activity-dependent manner. However, a stronger antiviral effect for AVI-4206 is observed in human airway organoids and peripheral blood monocyte-derived macrophages. In an animal model of severe SARS-CoV-2 infection, AVI-4206 reduces viral replication, potentiates innate immune responses, and leads to a survival benefit. Our results provide pharmacological proof of concept that Mac1 is a valid therapeutic target via a novel immune-restoring mechanism that could potentially synergize with existing therapies targeting distinct, essential aspects of the coronaviral life cycle. This approach could be more widely used to target other viral macrodomains to develop antiviral therapeutics beyond COVID-19.</jats:p>",
"alternative-id": [
"10.7554/eLife.103484"
],
"article-number": "RP103484",
"assertion": [
{
"group": {
"name": "peer_review_taxonomy"
},
"label": "Peer review transparency",
"name": "peer_review_transparency",
"value": "single anonymised"
},
{
"group": {
"name": "peer_review_taxonomy"
},
"label": "Peer review interaction",
"name": "peer_review_interaction",
"value": "other reviewer(s), editor"
},
{
"group": {
"name": "peer_review_taxonomy"
},
"label": "Peer review published",
"name": "peer_review_published",
"value": "review summaries, review reports, author/editor communication, reviewer identities reviewer opt in, editor identities"
},
{
"group": {
"name": "post_publication_commenting"
},
"label": "Post publication commenting",
"name": "post_publication_commenting",
"value": "open (sign in with ORCID iD required)"
}
],
"author": [
{
"ORCID": "https://orcid.org/0000-0001-8374-669X",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Gladstone Institute of Virology, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Suryawanshi",
"given": "Rahul K",
"sequence": "first"
},
{
"ORCID": "https://orcid.org/0009-0005-2013-8941",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Pharmaceutical Chemistry, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Jaishankar",
"given": "Priyadarshini",
"sequence": "first"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Bioengineering and Therapeutic Sciences, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"family": "Correy",
"given": "Galen J",
"sequence": "first"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Pharmaceutical Chemistry, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"family": "Rachman",
"given": "Moira M",
"sequence": "first"
},
{
"ORCID": "https://orcid.org/0000-0002-2919-5943",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Helen Diller Family Comprehensive Cancer Center, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "O'Leary",
"given": "Patrick C",
"sequence": "first"
},
{
"ORCID": "https://orcid.org/0000-0002-7344-7490",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Gladstone Institute of Virology, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Quantitative Biosciences Institute (QBI), University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Taha",
"given": "Taha Y",
"sequence": "first"
},
{
"ORCID": "https://orcid.org/0000-0002-6016-2867",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Gladstone Institute of Virology, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Matsui",
"given": "Yusuke",
"sequence": "first"
},
{
"ORCID": "https://orcid.org/0000-0002-2751-8411",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Gladstone Institute of Virology, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Zapatero-Belinchón",
"given": "Francisco J",
"sequence": "additional"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Gladstone Institute of Virology, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"family": "McCavitt-Malvido",
"given": "Maria",
"sequence": "additional"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Helen Diller Family Comprehensive Cancer Center, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"family": "Doruk",
"given": "Yagmur U",
"sequence": "additional"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Helen Diller Family Comprehensive Cancer Center, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"family": "Stevens",
"given": "Maisie GV",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0001-5900-3060",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Helen Diller Family Comprehensive Cancer Center, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Diolaiti",
"given": "Morgan E",
"sequence": "additional"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Helen Diller Family Comprehensive Cancer Center, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"family": "Jogalekar",
"given": "Manasi P",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0003-4681-0853",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Helen Diller Family Comprehensive Cancer Center, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Chen",
"given": "Huadong",
"sequence": "additional"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Quantitative Biosciences Institute (QBI), University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Cellular and Molecular Pharmacology, University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Data Science and Biotechnology Institute, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"family": "Richards",
"given": "Alicia L",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0003-1759-213X",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Quantitative Biosciences Institute (QBI), University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Cellular and Molecular Pharmacology, University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Data Science and Biotechnology Institute, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Kongpracha",
"given": "Pornparn",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-4046-7081",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Bioengineering and Therapeutic Sciences, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Bali",
"given": "Sofia",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-0353-0037",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Gladstone Institute of Virology, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Montano",
"given": "Mauricio",
"sequence": "additional"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Gladstone Institute of Virology, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"family": "Rosecrans",
"given": "Julia",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0003-3039-8155",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Data Science and Biotechnology Institute, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Matthay",
"given": "Michael",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0003-0243-0760",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Pharmaceutical Chemistry, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Togo",
"given": "Takaya",
"sequence": "additional"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Pharmaceutical Chemistry, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"family": "Gonciarz",
"given": "Ryan L",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0009-0003-6713-4492",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Quantitative Biosciences Institute (QBI), University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Gopalkrishnan",
"given": "Saumya",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-2247-9345",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Pharmaceutical Chemistry, University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Small Molecule Discovery Center, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Neitz",
"given": "R Jeffrey",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0003-4902-337X",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Bioengineering and Therapeutic Sciences, University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Quantitative Biosciences Institute (QBI), University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Data Science and Biotechnology Institute, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Krogan",
"given": "Nevan J",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0001-6119-6084",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Quantitative Biosciences Institute (QBI), University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Cellular and Molecular Pharmacology, University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Data Science and Biotechnology Institute, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Swaney",
"given": "Danielle L",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-6098-7367",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Pharmaceutical Chemistry, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Shoichet",
"given": "Brian K",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-5697-1274",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/038321296",
"id-type": "ROR"
}
],
"name": "Gladstone Institute of Virology, Gladstone Institutes",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Medicine, University of California San Francisco",
"place": [
"San Francisco, United States"
]
},
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/00knt4f32",
"id-type": "ROR"
}
],
"name": "Chan Zuckerberg Biohub- San Francisco, San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Ott",
"given": "Melanie",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-1240-2846",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Pharmaceutical Chemistry, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Renslo",
"given": "Adam R",
"sequence": "additional"
},
{
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Helen Diller Family Comprehensive Cancer Center, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"family": "Ashworth",
"given": "Alan",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-5080-2859",
"affiliation": [
{
"id": [
{
"asserted-by": "publisher",
"id": "https://ror.org/043mz5j54",
"id-type": "ROR"
}
],
"name": "Department of Bioengineering and Therapeutic Sciences, University of California San Francisco",
"place": [
"San Francisco, United States"
]
}
],
"authenticated-orcid": true,
"family": "Fraser",
"given": "James S",
"sequence": "additional"
}
],
"container-title": "eLife",
"content-domain": {
"crossmark-restriction": false,
"domain": [
"elifesciences.org"
]
},
"created": {
"date-parts": [
[
2025,
1,
6
]
],
"date-time": "2025-01-06T10:25:50Z",
"timestamp": 1736159150000
},
"deposited": {
"date-parts": [
[
2025,
11,
19
]
],
"date-time": "2025-11-19T15:35:44Z",
"timestamp": 1763566544000
},
"funder": [
{
"DOI": "10.13039/100000002",
"award": [
"U19AI171110"
],
"doi-asserted-by": "crossref",
"id": [
{
"asserted-by": "crossref",
"id": "10.13039/100000002",
"id-type": "DOI"
}
],
"name": "National Institutes of Health"
}
],
"indexed": {
"date-parts": [
[
2025,
11,
19
]
],
"date-time": "2025-11-19T15:39:29Z",
"timestamp": 1763566769087,
"version": "3.45.0"
},
"is-referenced-by-count": 1,
"issued": {
"date-parts": [
[
2025,
11,
19
]
]
},
"language": "en",
"license": [
{
"URL": "http://creativecommons.org/publicdomain/zero/1.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
11,
19
]
],
"date-time": "2025-11-19T00:00:00Z",
"timestamp": 1763510400000
}
},
{
"URL": "http://creativecommons.org/publicdomain/zero/1.0/",
"content-version": "am",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
11,
19
]
],
"date-time": "2025-11-19T00:00:00Z",
"timestamp": 1763510400000
}
},
{
"URL": "http://creativecommons.org/publicdomain/zero/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
11,
19
]
],
"date-time": "2025-11-19T00:00:00Z",
"timestamp": 1763510400000
}
}
],
"link": [
{
"URL": "https://cdn.elifesciences.org/articles/103484/elife-103484-v1.xml",
"content-type": "application/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://cdn.elifesciences.org/articles/103484/elife-103484-v1.pdf",
"content-type": "application/pdf",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://elifesciences.org/articles/103484",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "4374",
"original-title": [],
"prefix": "10.7554",
"published": {
"date-parts": [
[
2025,
11,
19
]
]
},
"published-online": {
"date-parts": [
[
2025,
11,
19
]
]
},
"publisher": "eLife Sciences Publications, Ltd",
"reference": [
{
"DOI": "10.1073/pnas.2302083120",
"article-title": "SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in mice",
"author": "Alhammad",
"doi-asserted-by": "publisher",
"journal-title": "PNAS",
"key": "bib1",
"type": "journal-article",
"volume": "120",
"year": "2023"
},
{
"DOI": "10.1038/s41586-020-2312-y",
"article-title": "The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice",
"author": "Bao",
"doi-asserted-by": "publisher",
"first-page": "830",
"journal-title": "Nature",
"key": "bib2",
"type": "journal-article",
"volume": "583",
"year": "2020"
},
{
"DOI": "10.1016/j.chom.2020.06.021",
"article-title": "Neutralizing Antibody and Soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2",
"author": "Case",
"doi-asserted-by": "publisher",
"first-page": "475",
"journal-title": "Cell Host & Microbe",
"key": "bib3",
"type": "journal-article",
"volume": "28",
"year": "2020"
},
{
"DOI": "10.1107/S205979831700331X",
"article-title": "Gentle, fast and effective crystal soaking by acoustic dispensing",
"author": "Collins",
"doi-asserted-by": "publisher",
"first-page": "246",
"journal-title": "Acta Crystallographica. Section D, Structural Biology",
"key": "bib4",
"type": "journal-article",
"volume": "73",
"year": "2017"
},
{
"DOI": "10.1126/sciadv.abo5083",
"article-title": "The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and x-ray diffraction at room temperature",
"author": "Correy",
"doi-asserted-by": "publisher",
"journal-title": "Science Advances",
"key": "bib5",
"type": "journal-article",
"volume": "8",
"year": "2022"
},
{
"DOI": "10.1126/sciadv.ads7187",
"article-title": "Exploration of structure-activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment linking and active learning",
"author": "Correy",
"doi-asserted-by": "publisher",
"journal-title": "Science Advances",
"key": "bib6",
"type": "journal-article",
"volume": "11",
"year": "2025"
},
{
"DOI": "10.1021/acschembio.1c00721",
"article-title": "High-throughput activity assay for screening inhibitors of the SARS-CoV-2 Mac1 Macrodomain",
"author": "Dasovich",
"doi-asserted-by": "publisher",
"first-page": "17",
"journal-title": "ACS Chemical Biology",
"key": "bib7",
"type": "journal-article",
"volume": "17",
"year": "2022"
},
{
"DOI": "10.1016/j.molcel.2023.04.009",
"article-title": "PARPs and ADP-ribosylation: Deciphering the complexity with molecular tools",
"author": "Dasovich",
"doi-asserted-by": "publisher",
"first-page": "1552",
"journal-title": "Molecular Cell",
"key": "bib8",
"type": "journal-article",
"volume": "83",
"year": "2023"
},
{
"DOI": "10.1107/S0907444913000061",
"article-title": "How good are my data and what is the resolution?",
"author": "Evans",
"doi-asserted-by": "publisher",
"first-page": "1204",
"journal-title": "Acta Crystallographica. Section D, Biological Crystallography",
"key": "bib9",
"type": "journal-article",
"volume": "69",
"year": "2013"
},
{
"DOI": "10.1073/pnas.2212931120",
"article-title": "Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2",
"author": "Gahbauer",
"doi-asserted-by": "publisher",
"journal-title": "PNAS",
"key": "bib10",
"type": "journal-article",
"volume": "120",
"year": "2023"
},
{
"DOI": "10.1371/journal.ppat.1007756",
"article-title": "The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression",
"author": "Grunewald",
"doi-asserted-by": "publisher",
"journal-title": "PLOS Pathogens",
"key": "bib11",
"type": "journal-article",
"volume": "15",
"year": "2019"
},
{
"DOI": "10.1016/j.it.2012.11.001",
"article-title": "Epigenetic regulation of macrophage polarization and function",
"author": "Ivashkiv",
"doi-asserted-by": "publisher",
"first-page": "216",
"journal-title": "Trends in Immunology",
"key": "bib12",
"type": "journal-article",
"volume": "34",
"year": "2013"
},
{
"DOI": "10.1107/S0907444909047337",
"article-title": "XDS",
"author": "Kabsch",
"doi-asserted-by": "publisher",
"first-page": "125",
"journal-title": "Acta Crystallographica. Section D, Biological Crystallography",
"key": "bib13",
"type": "journal-article",
"volume": "66",
"year": "2010"
},
{
"DOI": "10.1038/s44318-024-00126-0",
"article-title": "PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation",
"author": "Kar",
"doi-asserted-by": "publisher",
"first-page": "2929",
"journal-title": "The EMBO Journal",
"key": "bib14",
"type": "journal-article",
"volume": "43",
"year": "2024"
},
{
"DOI": "10.1371/journal.pone.0254022",
"article-title": "Selective monitoring of the protein-free ADP-ribose released by ADP-ribosylation reversal enzymes",
"author": "Kasson",
"doi-asserted-by": "publisher",
"journal-title": "PLOS ONE",
"key": "bib15",
"type": "journal-article",
"volume": "16",
"year": "2021"
},
{
"DOI": "10.1038/ni.1863",
"article-title": "The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors",
"author": "Kawai",
"doi-asserted-by": "publisher",
"first-page": "373",
"journal-title": "Nature Immunology",
"key": "bib16",
"type": "journal-article",
"volume": "11",
"year": "2010"
},
{
"DOI": "10.1128/jvi.00885-23",
"article-title": "PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell- and tissue-specific manner",
"author": "Kerr",
"doi-asserted-by": "publisher",
"journal-title": "Journal of Virology",
"key": "bib17",
"type": "journal-article",
"volume": "97",
"year": "2023"
},
{
"DOI": "10.1101/2024.01.03.574082",
"article-title": "Mutation of a highly conserved isoleucine residue in loop 2 of several β-Coronavirus macrodomains indicates that enhanced ADP-Ribose binding is detrimental to infection",
"author": "Kerr",
"doi-asserted-by": "publisher",
"key": "bib18",
"type": "preprint",
"volume-title": "bioRxiv",
"year": "2024"
},
{
"DOI": "10.1101/2024.03.05.583578",
"article-title": "Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants",
"author": "Khalid",
"doi-asserted-by": "publisher",
"key": "bib19",
"type": "preprint",
"volume-title": "bioRxiv",
"year": "2024"
},
{
"DOI": "10.1038/s12276-021-00592-0",
"article-title": "Type I and III interferon responses in SARS-CoV-2 infection",
"author": "Kim",
"doi-asserted-by": "publisher",
"first-page": "750",
"journal-title": "Experimental & Molecular Medicine",
"key": "bib20",
"type": "journal-article",
"volume": "53",
"year": "2021"
},
{
"DOI": "10.1101/2024.08.19.608619",
"article-title": "Discovery of Potent SARS-CoV-2 Nsp3 macrodomain inhibitors uncovers lack of translation to cellular antiviral response",
"author": "Lee",
"doi-asserted-by": "publisher",
"key": "bib21",
"type": "preprint",
"volume-title": "bioRxiv",
"year": "2024"
},
{
"DOI": "10.3390/pathogens11010094",
"article-title": "The conserved macrodomain is a potential therapeutic target for coronaviruses and alphaviruses",
"author": "Leung",
"doi-asserted-by": "publisher",
"journal-title": "Pathogens",
"key": "bib22",
"type": "journal-article",
"volume": "11",
"year": "2022"
},
{
"DOI": "10.1038/s41573-023-00672-y",
"article-title": "Therapeutic strategies for COVID-19: progress and lessons learned",
"author": "Li",
"doi-asserted-by": "publisher",
"first-page": "449",
"journal-title": "Nature Reviews. Drug Discovery",
"key": "bib23",
"type": "journal-article",
"volume": "22",
"year": "2023"
},
{
"DOI": "10.1073/pnas.2300376120",
"article-title": "Human airway and nasal organoids reveal escalating replicative fitness of SARS-CoV-2 emerging variants",
"author": "Li",
"doi-asserted-by": "publisher",
"journal-title": "PNAS",
"key": "bib24",
"type": "journal-article",
"volume": "120",
"year": "2023"
},
{
"DOI": "10.1107/S2059798319011471",
"article-title": "Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix",
"author": "Liebschner",
"doi-asserted-by": "publisher",
"first-page": "861",
"journal-title": "Acta Crystallographica. Section D, Structural Biology",
"key": "bib25",
"type": "journal-article",
"volume": "75",
"year": "2019"
},
{
"DOI": "10.1126/science.aam7344",
"article-title": "PARP inhibitors: Synthetic lethality in the clinic",
"author": "Lord",
"doi-asserted-by": "publisher",
"first-page": "1152",
"journal-title": "Science",
"key": "bib26",
"type": "journal-article",
"volume": "355",
"year": "2017"
},
{
"DOI": "10.1038/s41598-018-27834-y",
"article-title": "A widely-applicable high-throughput cellular thermal shift assay (CETSA) using split Nano Luciferase",
"author": "Martinez",
"doi-asserted-by": "publisher",
"journal-title": "Scientific Reports",
"key": "bib27",
"type": "journal-article",
"volume": "8",
"year": "2018"
},
{
"DOI": "10.1107/S0021889807021206",
"article-title": "Phaser crystallographic software",
"author": "McCoy",
"doi-asserted-by": "publisher",
"first-page": "658",
"journal-title": "Journal of Applied Crystallography",
"key": "bib28",
"type": "journal-article",
"volume": "40",
"year": "2007"
},
{
"DOI": "10.1021/acs.jproteome.0c00872",
"article-title": "Inflect: Optimizing computational workflows for thermal proteome profiling data analysis",
"author": "McCracken",
"doi-asserted-by": "publisher",
"first-page": "1874",
"journal-title": "Journal of Proteome Research",
"key": "bib29",
"type": "journal-article",
"volume": "20",
"year": "2021"
},
{
"DOI": "10.1073/pnas.1621485114",
"article-title": "ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical for virus replication and virulence",
"author": "McPherson",
"doi-asserted-by": "publisher",
"first-page": "1666",
"journal-title": "PNAS",
"key": "bib30",
"type": "journal-article",
"volume": "114",
"year": "2017"
},
{
"DOI": "10.1107/S2052252520009653",
"article-title": "Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes",
"author": "Michalska",
"doi-asserted-by": "publisher",
"first-page": "814",
"journal-title": "IUCrJ",
"key": "bib31",
"type": "journal-article",
"volume": "7",
"year": "2020"
},
{
"DOI": "10.1038/s41579-022-00839-1",
"article-title": "Innate immune evasion strategies of SARS-CoV-2",
"author": "Minkoff",
"doi-asserted-by": "publisher",
"first-page": "178",
"journal-title": "Nature Reviews. Microbiology",
"key": "bib32",
"type": "journal-article",
"volume": "21",
"year": "2023"
},
{
"DOI": "10.1038/s42003-021-02983-5",
"article-title": "SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB",
"author": "Neufeldt",
"doi-asserted-by": "publisher",
"journal-title": "Communications Biology",
"key": "bib33",
"type": "journal-article",
"volume": "5",
"year": "2022"
},
{
"DOI": "10.3390/pathogens12101221",
"article-title": "An update on the current state of SARS-CoV-2 Mac1 inhibitors",
"author": "O’Connor",
"doi-asserted-by": "publisher",
"journal-title": "Pathogens",
"key": "bib34",
"type": "journal-article",
"volume": "12",
"year": "2023"
},
{
"DOI": "10.1038/s41467-020-19891-7",
"article-title": "Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice",
"author": "Oladunni",
"doi-asserted-by": "publisher",
"journal-title": "Nature Communications",
"key": "bib35",
"type": "journal-article",
"volume": "11",
"year": "2020"
},
{
"DOI": "10.1073/pnas.2320713121",
"article-title": "Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid",
"author": "Papini",
"doi-asserted-by": "publisher",
"journal-title": "PNAS",
"key": "bib36",
"type": "journal-article",
"volume": "121",
"year": "2024"
},
{
"DOI": "10.1101/2024.04.26.591186",
"article-title": "PARP14 is an interferon (IFN)-induced host factor that promotes IFN production and affects the replication of multiple viruses",
"author": "Parthasarathy",
"doi-asserted-by": "publisher",
"key": "bib37",
"type": "preprint",
"volume-title": "bioRxiv",
"year": "2024"
},
{
"DOI": "10.1038/ncomms15123",
"article-title": "A multi-crystal method for extracting obscured crystallographic states from conventionally uninterpretable electron density",
"author": "Pearce",
"doi-asserted-by": "publisher",
"journal-title": "Nature Communications",
"key": "bib38",
"type": "journal-article",
"volume": "8",
"year": "2017"
},
{
"DOI": "10.1038/nri1604",
"article-title": "Mechanisms of type-I- and type-II-interferon-mediated signalling",
"author": "Platanias",
"doi-asserted-by": "publisher",
"first-page": "375",
"journal-title": "Nature Reviews. Immunology",
"key": "bib39",
"type": "journal-article",
"volume": "5",
"year": "2005"
},
{
"DOI": "10.1042/BSR20240986",
"article-title": "Interferon-induced ADP-ribosylation: technical developments driving ICAB discovery",
"author": "Ribeiro",
"doi-asserted-by": "publisher",
"journal-title": "Bioscience Reports",
"key": "bib40",
"type": "journal-article",
"volume": "45",
"year": "2025"
},
{
"DOI": "10.1038/s41467-023-40076-5",
"article-title": "Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19",
"author": "Robertson",
"doi-asserted-by": "publisher",
"journal-title": "Nature Communications",
"key": "bib41",
"type": "journal-article",
"volume": "14",
"year": "2023"
},
{
"DOI": "10.15252/embj.2018100300",
"article-title": "Long-term expanding human airway organoids for disease modeling",
"author": "Sachs",
"doi-asserted-by": "publisher",
"journal-title": "The EMBO Journal",
"key": "bib42",
"type": "journal-article",
"volume": "38",
"year": "2019"
},
{
"DOI": "10.1021/acschembio.2c00334",
"article-title": "Real-time cellular thermal shift assay to monitor target engagement",
"author": "Sanchez",
"doi-asserted-by": "publisher",
"first-page": "2471",
"journal-title": "ACS Chemical Biology",
"key": "bib43",
"type": "journal-article",
"volume": "17",
"year": "2022"
},
{
"DOI": "10.1126/science.1255784",
"article-title": "Tracking cancer drugs in living cells by thermal profiling of the proteome",
"author": "Savitski",
"doi-asserted-by": "publisher",
"journal-title": "Science",
"key": "bib44",
"type": "journal-article",
"volume": "346",
"year": "2014"
},
{
"DOI": "10.1126/sciadv.abf8711",
"article-title": "Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking",
"author": "Schuller",
"doi-asserted-by": "publisher",
"journal-title": "Science Advances",
"key": "bib45",
"type": "journal-article",
"volume": "7",
"year": "2021"
},
{
"DOI": "10.3390/pathogens12020324",
"article-title": "Discovery and development strategies for SARS-CoV-2 NSP3 macrodomain inhibitors",
"author": "Schuller",
"doi-asserted-by": "publisher",
"journal-title": "Pathogens",
"key": "bib46",
"type": "journal-article",
"volume": "12",
"year": "2023"
},
{
"DOI": "10.1038/s41586-022-04802-1",
"article-title": "Inflammasome activation in infected macrophages drives COVID-19 pathology",
"author": "Sefik",
"doi-asserted-by": "publisher",
"first-page": "585",
"journal-title": "Nature",
"key": "bib47",
"type": "journal-article",
"volume": "606",
"year": "2022"
},
{
"DOI": "10.1016/j.cell.2018.10.024",
"article-title": "Genome-wide CRISPR screens in primary human T cells reveal key regulators of immune function",
"author": "Shifrut",
"doi-asserted-by": "publisher",
"first-page": "1958",
"journal-title": "Cell",
"key": "bib48",
"type": "journal-article",
"volume": "175",
"year": "2018"
},
{
"DOI": "10.1038/s41598-024-66003-2",
"article-title": "NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids",
"author": "Simoneau",
"doi-asserted-by": "publisher",
"journal-title": "Scientific Reports",
"key": "bib49",
"type": "journal-article",
"volume": "14",
"year": "2024"
},
{
"DOI": "10.1101/gad.334516.119",
"article-title": "PARP and PARG inhibitors in cancer treatment",
"author": "Slade",
"doi-asserted-by": "publisher",
"first-page": "360",
"journal-title": "Genes & Development",
"key": "bib50",
"type": "journal-article",
"volume": "34",
"year": "2020"
},
{
"DOI": "10.1038/s41586-022-04865-0",
"article-title": "Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination",
"author": "Suryawanshi",
"doi-asserted-by": "publisher",
"first-page": "351",
"journal-title": "Nature",
"key": "bib51",
"type": "journal-article",
"volume": "607",
"year": "2022"
},
{
"DOI": "10.1038/s41467-023-37787-0",
"article-title": "Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6",
"author": "Taha",
"doi-asserted-by": "publisher",
"journal-title": "Nature Communications",
"key": "bib52",
"type": "journal-article",
"volume": "14",
"year": "2023"
},
{
"DOI": "10.1371/journal.ppat.1011614",
"article-title": "A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo",
"author": "Taha",
"doi-asserted-by": "publisher",
"journal-title": "PLOS Pathogens",
"key": "bib53",
"type": "journal-article",
"volume": "19",
"year": "2023"
},
{
"DOI": "10.1126/science.adm9724",
"article-title": "Design of a SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model",
"author": "Tan",
"doi-asserted-by": "publisher",
"first-page": "1434",
"journal-title": "Science",
"key": "bib54",
"type": "journal-article",
"volume": "383",
"year": "2024"
},
{
"DOI": "10.1038/s41573-023-00692-8",
"article-title": "Accelerating antiviral drug discovery: lessons from COVID-19",
"author": "von Delft",
"doi-asserted-by": "publisher",
"first-page": "585",
"journal-title": "Nature Reviews. Drug Discovery",
"key": "bib55",
"type": "journal-article",
"volume": "22",
"year": "2023"
},
{
"DOI": "10.1021/acs.orglett.8b01742",
"article-title": "Synthetic α- and β-Ser-ADP-ribosylated Peptides Reveal α-Ser-ADPr as the Native Epimer",
"author": "Voorneveld",
"doi-asserted-by": "publisher",
"first-page": "4140",
"journal-title": "Organic Letters",
"key": "bib56",
"type": "journal-article",
"volume": "20",
"year": "2018"
},
{
"DOI": "10.1128/JVI.00766-21",
"article-title": "Unique mutations in the murine hepatitis virus macrodomain differentially attenuate virus replication, indicating multiple roles for the macrodomain in coronavirus replication",
"author": "Voth",
"doi-asserted-by": "publisher",
"journal-title": "Journal of Virology",
"key": "bib57",
"type": "journal-article",
"volume": "95",
"year": "2021"
},
{
"DOI": "10.1021/acs.jmedchem.3c02451",
"article-title": "Discovery of 2-Amide-3-methylester Thiophenes that Target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an Antiviral Target",
"author": "Wazir",
"doi-asserted-by": "publisher",
"first-page": "6519",
"journal-title": "Journal of Medicinal Chemistry",
"key": "bib58",
"type": "journal-article",
"volume": "67",
"year": "2024"
},
{
"DOI": "10.1016/j.chom.2020.04.004",
"article-title": "An infectious cDNA clone of SARS-CoV-2",
"author": "Xie",
"doi-asserted-by": "publisher",
"first-page": "841",
"journal-title": "Cell Host & Microbe",
"key": "bib59",
"type": "journal-article",
"volume": "27",
"year": "2020"
},
{
"DOI": "10.1038/s41586-020-2943-z",
"article-title": "COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice",
"author": "Zheng",
"doi-asserted-by": "publisher",
"first-page": "603",
"journal-title": "Nature",
"key": "bib60",
"type": "journal-article",
"volume": "589",
"year": "2021"
},
{
"DOI": "10.2210/pdb9cxy/pdb",
"article-title": "9CXY - Crystal structure of SARS-CoV-2 NSP3 macrodomain in complex with AVI-1500",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset1",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. 9CXY - Crystal structure of SARS-CoV-2 NSP3 macrodomain in complex with AVI-1500. Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
},
{
"DOI": "10.2210/pdb9cxz/pdb",
"article-title": "9CXZ - Crystal structure of SARS-CoV-2 NSP3 macrodomain in complex with AVI-1501",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset2",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. 9CXZ - Crystal structure of SARS-CoV-2 NSP3 macrodomain in complex with AVI-1501. Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
},
{
"DOI": "10.2210/pdb7hc4/pdb",
"article-title": "PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3367",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset3",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3367. Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
},
{
"DOI": "10.2210/pdb7hc5/pdb",
"article-title": "PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3765",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset4",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3765. Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
},
{
"DOI": "10.2210/pdb7hc6/pdb",
"article-title": "PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3764",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset5",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3764. Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
},
{
"DOI": "10.2210/pdb7hc7/pdb",
"article-title": "PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-4051",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset6",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-4051. Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
},
{
"DOI": "10.2210/pdb7hc8/pdb",
"article-title": "PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3763",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset7",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3763. Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
},
{
"DOI": "10.2210/pdb7hc9/pdb",
"article-title": "PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3762",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset8",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-3762. Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
},
{
"DOI": "10.2210/pdb7hca/pdb",
"article-title": "PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-4636",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset9",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. PanDDA analysis group deposition -- Crystal structure of SARS-CoV-2 NSP3 macrodmain in complex with AVI-4636. Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
},
{
"DOI": "10.2210/pdb9cy0/pdb",
"article-title": "PDB Entry - 9CY0 (pdb_00009cy0)",
"author": "Correy",
"doi-asserted-by": "publisher",
"key": "dataset10",
"type": "dataset",
"unstructured": "Correy GJ, Fraser JS. 2025. PDB Entry - 9CY0 (pdb_00009cy0). Worldwide Protein Data Bank.",
"volume-title": "Worldwide Protein Data Bank",
"year": "2025"
}
],
"reference-count": 70,
"references-count": 70,
"relation": {
"has-preprint": [
{
"asserted-by": "subject",
"id": "10.1101/2024.08.08.606661",
"id-type": "doi"
}
],
"is-same-as": [
{
"asserted-by": "subject",
"id": "10.7554/eLife.103484.3",
"id-type": "doi"
}
],
"is-supplemented-by": [
{
"asserted-by": "subject",
"id": "10.2210/pdb9cxy/pdb",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.2210/pdb9cxz/pdb",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.2210/pdb7hc4/pdb",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.2210/pdb7hc5/pdb",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.2210/pdb7hc6/pdb",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.2210/pdb7hc7/pdb",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.2210/pdb7hc8/pdb",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.2210/pdb7hc9/pdb",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.2210/pdb7hca/pdb",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.2210/pdb9cy0/pdb",
"id-type": "doi"
}
],
"is-version-of": [
{
"asserted-by": "subject",
"id": "10.7554/eLife.103484.1",
"id-type": "doi"
},
{
"asserted-by": "subject",
"id": "10.7554/eLife.103484.2",
"id-type": "doi"
}
]
},
"resource": {
"primary": {
"URL": "https://elifesciences.org/articles/103484"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "The Mac1 ADP-ribosylhydrolase is a therapeutic target for SARS-CoV-2",
"type": "journal-article",
"update-policy": "https://doi.org/10.7554/elife.103484",
"volume": "14"
}