Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response
et al., iScience, doi:10.1016/j.isci.2026.115038, Mar 2026
In vitro and mouse study showing benefit of PAD4 inhibition with GSK199 and BB-Cl-amidine against SARS-CoV-2 infection.
Pasquero et al., 31 Mar 2026, Italy, peer-reviewed, 21 authors, study period 6 January, 2025 - 2 February, 2025.
Contact: marco.deandrea@unito.it (corresponding author), marco.deandrea@unito.it (corresponding author).
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Check
SARS-CoV-2 infection
PAD4 targeting halts induces citrullination
In vitro
SARS-CoV-2 replication
iScience
In vivo
Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response
Graphical abstract
Aberrant citrullination
Hyperinflammation and cytokine storm
Highlights
- SARS-CoV-2 variants upregulate PAD4 in human cells and mouse lungs and brain
- 170 proteins are differentially citrullinated in vivo upon SARSCoV-2 infection
- The PAD4-inhibitor GSK199 limits viral replication and inflammation in vitro and in vivo
- PAD2 is significantly downregulated in the brains of SARSCoV-2-infected mice
Authors
Selina Pasquero, Alessandro Penna, Lucia Signorini, ..., Paul R. Thompson, Antonio Rosato, Marco De Andrea
Correspondence
[marco.deandrea@unito.it](mailto:marco.deandrea@unito.it)
In brief
Natural sciences; Biological sciences; Microbiology; Virology
Normalized citrullination
iScience
Article
Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response
Selina Pasquero, 1 Alessandro Penna, 2 Lucia Signorini, 3 Salvatore Villani, 4 Francesca Gugliesi, 1 Valeria Caneparo, 5 Francesco Favero, 5 Webb Camille, 6 Robert M. Green, 6 Ilaria Frasson, 7 Anna Tosi, 8 Beatrice Genova, 8 Anna Dalla Pieta ` , 2 Ranieri Verin, 9 Sofia Tomasoni, 9 Erika Del Grosso, 4 Serena Delbue, 3 Sara N. Richter, 7,10 Paul R. Thompson, 6 Antonio Rosato, 2,8 and Marco De Andrea 1,5,11, *
1 Department of Public Health and Pediatric Sciences, University of Turin -Medical School, Turin, Italy
2 Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
3
Department of
Biomedical,
Surgical and
Dental
Sciences,
University of
Milan,
Milan,
Italy
4 Department of Pharmaceutical Sciences, University of Eastern Piedmont, Novara, Italy
5 CAAD Center for Translational Research on Autoimmune and Allergic Disease, University of Eastern Piedmont, Novara Medical School, Novara, Italy
6 Department of Biochemistry and Molecular Pharmacology, UMass Medical School, Worcester, MA, USA
7 Department of Molecular Medicine, University of Padua, Padua, Italy
8 Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
9 Department of Comparative Biomedicine and Food Science, University of Padua, Padua, Italy
10 Microbiology and Virology Unit, Padua University Hospital, 35128 Padua, Italy
11 Lead contact
*Correspondence:
marco.deandrea@unito.it
https://doi.org/10.1016/j.isci.2026.115038
SUMMARY
SARS-CoV-2, the causative agent of COVID-19, remains a global concern due to gaps in understanding its pathogenesis. Peptidyl-arginine deiminases (PADs) are emerging as key regulators of viral replication and inflammation. PADs catalyze the conversion of arginine into citrulline, a modification linked to autoimmune diseases. Here, we show that PAD-mediated citrullination plays a crucial role in SARS-CoV-2 infection. Using human cell lines and in K18-hACE2 transgenic mice infected with different SARS-CoV-2 strains, we demonstrate that viral replication is associated with increased PAD4 expression. Mass spectrometry shows 170 distinct differentially citrullinated proteins in infected cells and tissues. Importantly, PAD4 inhibition significantly reduces viral replication and restores a citrullination profile comparable to that of uninfected mice. These fi ndings suggest that SARS-CoV-2..
DOI record:
{
"DOI": "10.1016/j.isci.2026.115038",
"ISSN": [
"2589-0042"
],
"URL": "http://dx.doi.org/10.1016/j.isci.2026.115038",
"alternative-id": [
"S258900422600413X"
],
"article-number": "115038",
"assertion": [
{
"label": "This article is maintained by",
"name": "publisher",
"value": "Elsevier"
},
{
"label": "Article Title",
"name": "articletitle",
"value": "Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response"
},
{
"label": "Journal Title",
"name": "journaltitle",
"value": "iScience"
},
{
"label": "CrossRef DOI link to publisher maintained version",
"name": "articlelink",
"value": "https://doi.org/10.1016/j.isci.2026.115038"
},
{
"label": "Content Type",
"name": "content_type",
"value": "article"
},
{
"label": "Copyright",
"name": "copyright",
"value": "© 2026 The Author(s). Published by Elsevier Inc."
}
],
"author": [
{
"affiliation": [],
"family": "Pasquero",
"given": "Selina",
"sequence": "first"
},
{
"affiliation": [],
"family": "Penna",
"given": "Alessandro",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Signorini",
"given": "Lucia",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Villani",
"given": "Salvatore",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Gugliesi",
"given": "Francesca",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Caneparo",
"given": "Valeria",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Favero",
"given": "Francesco",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Camille",
"given": "Webb",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Green",
"given": "Robert M.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Frasson",
"given": "Ilaria",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Tosi",
"given": "Anna",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Genova",
"given": "Beatrice",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Pietà",
"given": "Anna Dalla",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Verin",
"given": "Ranieri",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Tomasoni",
"given": "Sofia",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Del Grosso",
"given": "Erika",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Delbue",
"given": "Serena",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Richter",
"given": "Sara N.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Thompson",
"given": "Paul R.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Rosato",
"given": "Antonio",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0002-3188-5783",
"affiliation": [],
"authenticated-orcid": false,
"family": "De Andrea",
"given": "Marco",
"sequence": "additional"
}
],
"container-title": "iScience",
"container-title-short": "iScience",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"cell.com",
"elsevier.com",
"sciencedirect.com"
]
},
"created": {
"date-parts": [
[
2026,
2,
17
]
],
"date-time": "2026-02-17T08:11:11Z",
"timestamp": 1771315871000
},
"deposited": {
"date-parts": [
[
2026,
4,
1
]
],
"date-time": "2026-04-01T17:46:07Z",
"timestamp": 1775065567000
},
"funder": [
{
"DOI": "10.13039/100007402",
"award": [
"ROSA_CARIVARI20_01"
],
"award-info": [
{
"award-number": [
"ROSA_CARIVARI20_01"
]
}
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100007402",
"id-type": "DOI"
}
],
"name": "Caterpillar Foundation"
},
{
"DOI": "10.13039/100010661",
"award": [
"hCoV-19/Netherlands/NH-RIVM-27142/2021_P2"
],
"award-info": [
{
"award-number": [
"hCoV-19/Netherlands/NH-RIVM-27142/2021_P2"
]
}
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100010661",
"id-type": "DOI"
}
],
"name": "Horizon 2020 Framework Programme"
},
{
"DOI": "10.13039/100010661",
"award": [
"871029"
],
"award-info": [
{
"award-number": [
"871029"
]
}
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100010661",
"id-type": "DOI"
}
],
"name": "Horizon 2020 Framework Programme"
},
{
"DOI": "10.13039/501100021856",
"award": [
"2022 HERMIA"
],
"award-info": [
{
"award-number": [
"2022 HERMIA"
]
}
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100021856",
"id-type": "DOI"
}
],
"name": "Ministero dell'Università e della Ricerca"
},
{
"DOI": "10.13039/501100021856",
"award": [
"PNRR 2022 P20225P4T7"
],
"award-info": [
{
"award-number": [
"PNRR 2022 P20225P4T7"
]
}
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100021856",
"id-type": "DOI"
}
],
"name": "Ministero dell'Università e della Ricerca"
},
{
"DOI": "10.13039/501100003407",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100003407",
"id-type": "DOI"
}
],
"name": "Ministero dell’Istruzione, dell’Università e della Ricerca"
},
{
"DOI": "10.13039/100007479",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100007479",
"id-type": "DOI"
}
],
"name": "Foundation of the Savings Bank of Padua and Rovigo"
},
{
"DOI": "10.13039/501100004710",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100004710",
"id-type": "DOI"
}
],
"name": "Fondazione Umberto Veronesi"
},
{
"DOI": "10.13039/501100000780",
"award": [
"PE00000007"
],
"award-info": [
{
"award-number": [
"PE00000007"
]
}
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100000780",
"id-type": "DOI"
}
],
"name": "Commission européenne"
},
{
"DOI": "10.13039/501100024370",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100024370",
"id-type": "DOI"
}
],
"name": "Governo Italiano Ministero dell'Istruzione dell'Università e della Ricerca"
},
{
"DOI": "10.13039/501100006692",
"award": [
"RILO2024"
],
"award-info": [
{
"award-number": [
"RILO2024"
]
}
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100006692",
"id-type": "DOI"
}
],
"name": "Università degli Studi di Torino"
},
{
"DOI": "10.13039/501100006692",
"award": [
"RILO2023"
],
"award-info": [
{
"award-number": [
"RILO2023"
]
}
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100006692",
"id-type": "DOI"
}
],
"name": "Università degli Studi di Torino"
},
{
"DOI": "10.13039/100000002",
"award": [
"R35 GM118112"
],
"award-info": [
{
"award-number": [
"R35 GM118112"
]
}
],
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100000002",
"id-type": "DOI"
}
],
"name": "National Institutes of Health"
}
],
"indexed": {
"date-parts": [
[
2026,
4,
1
]
],
"date-time": "2026-04-01T19:00:35Z",
"timestamp": 1775070035128,
"version": "3.50.1"
},
"is-referenced-by-count": 0,
"issue": "3",
"issued": {
"date-parts": [
[
2026,
3
]
]
},
"journal-issue": {
"issue": "3",
"published-print": {
"date-parts": [
[
2026,
3
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://www.elsevier.com/tdm/userlicense/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2026,
3,
1
]
],
"date-time": "2026-03-01T00:00:00Z",
"timestamp": 1772323200000
}
},
{
"URL": "https://www.elsevier.com/legal/tdmrep-license",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2026,
3,
1
]
],
"date-time": "2026-03-01T00:00:00Z",
"timestamp": 1772323200000
}
},
{
"URL": "http://creativecommons.org/licenses/by-nc-nd/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2026,
2,
12
]
],
"date-time": "2026-02-12T00:00:00Z",
"timestamp": 1770854400000
}
}
],
"link": [
{
"URL": "https://api.elsevier.com/content/article/PII:S258900422600413X?httpAccept=text/xml",
"content-type": "text/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://api.elsevier.com/content/article/PII:S258900422600413X?httpAccept=text/plain",
"content-type": "text/plain",
"content-version": "vor",
"intended-application": "text-mining"
}
],
"member": "78",
"original-title": [],
"page": "115038",
"prefix": "10.1016",
"published": {
"date-parts": [
[
2026,
3
]
]
},
"published-print": {
"date-parts": [
[
2026,
3
]
]
},
"publisher": "Elsevier BV",
"reference": [
{
"DOI": "10.1016/S2213-2600(20)30076-X",
"article-title": "Pathological findings of COVID-19 associated with acute respiratory distress syndrome",
"author": "Xu",
"doi-asserted-by": "crossref",
"first-page": "420",
"journal-title": "Lancet Respir. Med.",
"key": "10.1016/j.isci.2026.115038_bib1",
"volume": "8",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)30251-8",
"article-title": "Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding",
"author": "Lu",
"doi-asserted-by": "crossref",
"first-page": "565",
"journal-title": "Lancet",
"key": "10.1016/j.isci.2026.115038_bib2",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1056/NEJMoa2007764",
"article-title": "Remdesivir for the Treatment of Covid-19 — Final Report",
"author": "Beigel",
"doi-asserted-by": "crossref",
"first-page": "1813",
"journal-title": "N. Engl. J. Med.",
"key": "10.1016/j.isci.2026.115038_bib3",
"volume": "383",
"year": "2020"
},
{
"DOI": "10.1126/scitranslmed.abl7430",
"article-title": "A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus",
"author": "Fischer",
"doi-asserted-by": "crossref",
"first-page": "eabl7430",
"journal-title": "Sci. Transl. Med.",
"key": "10.1016/j.isci.2026.115038_bib4",
"volume": "14",
"year": "2022"
},
{
"article-title": "A comprehensive review on COVID-19 vaccines: development, effectiveness, adverse effects, distribution and challenges",
"author": "Rahman",
"first-page": "1",
"journal-title": "Virus Dis.",
"key": "10.1016/j.isci.2026.115038_bib5",
"volume": "33",
"year": "2022"
},
{
"DOI": "10.7554/eLife.86002",
"article-title": "Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)",
"author": "Sherif",
"doi-asserted-by": "crossref",
"first-page": "e86002",
"journal-title": "eLife",
"key": "10.1016/j.isci.2026.115038_bib7",
"volume": "12",
"year": "2023"
},
{
"DOI": "10.1016/S0140-6736(20)30183-5",
"article-title": "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China",
"author": "Huang",
"doi-asserted-by": "crossref",
"first-page": "497",
"journal-title": "Lancet",
"key": "10.1016/j.isci.2026.115038_bib8",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1186/s40001-023-01293-2",
"article-title": "Neurological manifestations of SARS-CoV-2: complexity, mechanism and associated disorders",
"author": "Tyagi",
"doi-asserted-by": "crossref",
"first-page": "307",
"journal-title": "Eur. J. Med. Res.",
"key": "10.1016/j.isci.2026.115038_bib9",
"volume": "28",
"year": "2023"
},
{
"DOI": "10.1038/s41392-021-00679-0",
"article-title": "The signal pathways and treatment of cytokine storm in COVID-19",
"author": "Yang",
"doi-asserted-by": "crossref",
"first-page": "255",
"journal-title": "Signal Transduct. Target. Ther.",
"key": "10.1016/j.isci.2026.115038_bib10",
"volume": "6",
"year": "2021"
},
{
"DOI": "10.1038/s41577-021-00536-9",
"article-title": "Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19",
"author": "Bonaventura",
"doi-asserted-by": "crossref",
"first-page": "319",
"journal-title": "Nat. Rev. Immunol.",
"key": "10.1016/j.isci.2026.115038_bib11",
"volume": "21",
"year": "2021"
},
{
"DOI": "10.1016/j.eclinm.2023.101981",
"article-title": "Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: a retrospective cohort study",
"author": "Sun",
"doi-asserted-by": "crossref",
"journal-title": "eClinicalMedicine",
"key": "10.1016/j.isci.2026.115038_bib12",
"volume": "59",
"year": "2023"
},
{
"DOI": "10.1126/science.abl4784",
"article-title": "An oral SARS-CoV-2 M Mpro inhibitor clinical candidate for the treatment of COVID-19",
"author": "Owen",
"doi-asserted-by": "crossref",
"first-page": "1586",
"journal-title": "Science",
"key": "10.1016/j.isci.2026.115038_bib13",
"volume": "374",
"year": "2021"
},
{
"DOI": "10.1021/acs.jmedchem.2c00117",
"article-title": "Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19",
"author": "Unoh",
"doi-asserted-by": "crossref",
"first-page": "6499",
"journal-title": "J. Med. Chem.",
"key": "10.1016/j.isci.2026.115038_bib14",
"volume": "65",
"year": "2022"
},
{
"DOI": "10.1038/s41467-022-29104-y",
"article-title": "De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report",
"author": "Gandhi",
"doi-asserted-by": "crossref",
"first-page": "1547",
"journal-title": "Nat. Commun.",
"key": "10.1016/j.isci.2026.115038_bib15",
"volume": "13",
"year": "2022"
},
{
"DOI": "10.1038/s41586-022-05514-2",
"article-title": "Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir",
"author": "Iketani",
"doi-asserted-by": "crossref",
"first-page": "558",
"journal-title": "Nature",
"key": "10.1016/j.isci.2026.115038_bib16",
"volume": "613",
"year": "2023"
},
{
"DOI": "10.1016/j.cell.2022.12.018",
"article-title": "Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "279",
"journal-title": "Cell",
"key": "10.1016/j.isci.2026.115038_bib17",
"volume": "186",
"year": "2023"
},
{
"DOI": "10.1016/j.chom.2022.11.012",
"article-title": "Enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2",
"author": "Qu",
"doi-asserted-by": "crossref",
"first-page": "9",
"journal-title": "Cell Host Microbe",
"key": "10.1016/j.isci.2026.115038_bib18",
"volume": "31",
"year": "2023"
},
{
"DOI": "10.3390/ijms22010323",
"article-title": "Role of host-mediated post-translational modifications (PTMS) in RNA virus pathogenesis",
"author": "Kumar",
"doi-asserted-by": "crossref",
"first-page": "323",
"journal-title": "Int. J. Mol. Sci.",
"key": "10.1016/j.isci.2026.115038_bib19",
"volume": "22",
"year": "2020"
},
{
"DOI": "10.1002/art.21629",
"article-title": "Deiminated Epstein-Barr virus nuclear antigen 1 is a target of anti-citrullinated protein antibodies in rheumatoid arthritis",
"author": "Pratesi",
"doi-asserted-by": "crossref",
"first-page": "733",
"journal-title": "Arthritis Rheum.",
"key": "10.1016/j.isci.2026.115038_bib20",
"volume": "54",
"year": "2006"
},
{
"DOI": "10.3389/fimmu.2020.00085",
"article-title": "Citrullination Alters the Antiviral and Immunomodulatory Activities of the Human Cathelicidin LL-37 During Rhinovirus Infection",
"author": "Casanova",
"doi-asserted-by": "crossref",
"journal-title": "Front. Immunol.",
"key": "10.1016/j.isci.2026.115038_bib21",
"volume": "11",
"year": "2020"
},
{
"DOI": "10.1038/s41467-021-24178-6",
"article-title": "Human cytomegalovirus-induced host protein citrullination is crucial for viral replication",
"author": "Griffante",
"doi-asserted-by": "crossref",
"first-page": "3910",
"journal-title": "Nat. Commun.",
"key": "10.1016/j.isci.2026.115038_bib22",
"volume": "12",
"year": "2021"
},
{
"DOI": "10.1016/j.antiviral.2022.105278",
"article-title": "Novel antiviral activity of PAD inhibitors against human beta-coronaviruses HCoV-OC43 and SARS-CoV-2",
"author": "Pasquero",
"doi-asserted-by": "crossref",
"journal-title": "Antiviral Res.",
"key": "10.1016/j.isci.2026.115038_bib23",
"volume": "200",
"year": "2022"
},
{
"DOI": "10.3390/antib11010020",
"article-title": "Reactivity of Rheumatoid Arthritis-Associated Citrulline-Dependent Antibodies to Epstein-Barr Virus Nuclear Antigen1-3",
"author": "Fanelli",
"doi-asserted-by": "crossref",
"first-page": "15",
"journal-title": "Antibodies",
"key": "10.1016/j.isci.2026.115038_bib24",
"volume": "11",
"year": "2022"
},
{
"DOI": "10.1371/journal.ppat.1011849",
"article-title": "Citrullination profile analysis reveals peptidylarginine deaminase 3 as an HSV-1 target to dampen the activity of candidate antiviral restriction factors",
"author": "Pasquero",
"doi-asserted-by": "crossref",
"journal-title": "PLoS Path",
"key": "10.1016/j.isci.2026.115038_bib25",
"volume": "19",
"year": "2023"
},
{
"DOI": "10.1002/bies.10357",
"article-title": "PAD, a growing family of citrullinating enzymes: Genes, features and involvement in disease",
"author": "Vossenaar",
"doi-asserted-by": "crossref",
"first-page": "1106",
"journal-title": "Bioessays",
"key": "10.1016/j.isci.2026.115038_bib26",
"volume": "25",
"year": "2003"
},
{
"DOI": "10.1016/j.tcb.2022.01.014",
"article-title": "Insights into peptidylarginine deiminase expression and citrullination pathways",
"author": "Yu",
"doi-asserted-by": "crossref",
"first-page": "746",
"journal-title": "Trends Cell Biol.",
"key": "10.1016/j.isci.2026.115038_bib27",
"volume": "32",
"year": "2022"
},
{
"DOI": "10.1016/j.celrep.2019.03.108",
"article-title": "PAD2-Mediated Citrullination Contributes to Efficient Oligodendrocyte Differentiation and Myelination",
"author": "Falcão",
"doi-asserted-by": "crossref",
"first-page": "1090",
"journal-title": "Cell Rep.",
"key": "10.1016/j.isci.2026.115038_bib28",
"volume": "27",
"year": "2019"
},
{
"DOI": "10.1038/nature12942",
"article-title": "Citrullination regulates pluripotency and histone H1 binding to chromatin",
"author": "Christophorou",
"doi-asserted-by": "crossref",
"first-page": "104",
"journal-title": "Nature",
"key": "10.1016/j.isci.2026.115038_bib29",
"volume": "507",
"year": "2014"
},
{
"DOI": "10.4049/jimmunol.180.3.1895",
"article-title": "Histone deimination as a response to inflammatory stimuli in neutrophils",
"author": "Neeli",
"doi-asserted-by": "crossref",
"first-page": "1895",
"journal-title": "J. Immunol.",
"key": "10.1016/j.isci.2026.115038_bib30",
"volume": "180",
"year": "2008"
},
{
"DOI": "10.1016/j.chembiol.2018.03.002",
"article-title": "The Rheumatoid Arthritis-Associated Citrullinome",
"author": "Tilvawala",
"doi-asserted-by": "crossref",
"first-page": "691",
"journal-title": "Cell Chem. Biol.",
"key": "10.1016/j.isci.2026.115038_bib31",
"volume": "25",
"year": "2018"
},
{
"DOI": "10.1158/0008-5472.CAN-18-2797",
"article-title": "Citrullination in Cancer",
"author": "Yuzhalin",
"doi-asserted-by": "crossref",
"first-page": "1274",
"journal-title": "Cancer Res.",
"key": "10.1016/j.isci.2026.115038_bib32",
"volume": "79",
"year": "2019"
},
{
"DOI": "10.1073/pnas.1721115115",
"article-title": "Biochemically altered myelin triggers autoimmune demyelination",
"author": "Caprariello",
"doi-asserted-by": "crossref",
"first-page": "5528",
"journal-title": "Proc. Natl. Acad. Sci. USA",
"key": "10.1016/j.isci.2026.115038_bib33",
"volume": "115",
"year": "2018"
},
{
"DOI": "10.1007/s00018-022-04126-3",
"article-title": "Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives",
"author": "Ciesielski",
"doi-asserted-by": "crossref",
"first-page": "20",
"journal-title": "Cell. Mol. Life Sci.",
"key": "10.1016/j.isci.2026.115038_bib34",
"volume": "79",
"year": "2022"
},
{
"DOI": "10.1136/annrheumdis-2014-205365",
"article-title": "Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice",
"author": "Knight",
"doi-asserted-by": "crossref",
"first-page": "2199",
"journal-title": "Ann. Rheum. Dis.",
"key": "10.1016/j.isci.2026.115038_bib35",
"volume": "74",
"year": "2015"
},
{
"DOI": "10.4049/jimmunol.1001620",
"article-title": "N-α-Benzoyl-N5-(2-Chloro-1-Iminoethyl)-l-Ornithine Amide, a Protein Arginine Deiminase Inhibitor, Reduces the Severity of Murine Collagen-Induced Arthritis",
"author": "Willis",
"doi-asserted-by": "crossref",
"first-page": "4396",
"journal-title": "J. Immunol.",
"key": "10.1016/j.isci.2026.115038_bib36",
"volume": "186",
"year": "2011"
},
{
"DOI": "10.1038/nchembio.1735",
"article-title": "Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation",
"author": "Lewis",
"doi-asserted-by": "crossref",
"first-page": "189",
"journal-title": "Nat. Chem. Biol.",
"key": "10.1016/j.isci.2026.115038_bib37",
"volume": "11",
"year": "2015"
},
{
"DOI": "10.3389/fimmu.2021.716250",
"article-title": "Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 (PAD2) and PAD4",
"author": "Martín Monreal",
"doi-asserted-by": "crossref",
"first-page": "1",
"journal-title": "Front. Immunol.",
"key": "10.1016/j.isci.2026.115038_bib38",
"volume": "12",
"year": "2021"
},
{
"DOI": "10.1159/000448808",
"article-title": "Cl-Amidine Prevents Histone 3 Citrullination and Neutrophil Extracellular Trap Formation, and Improves Survival in a Murine Sepsis Model",
"author": "Biron",
"doi-asserted-by": "crossref",
"first-page": "22",
"journal-title": "J. Innate Immun.",
"key": "10.1016/j.isci.2026.115038_bib39",
"volume": "9",
"year": "2017"
},
{
"DOI": "10.1111/cei.12932",
"article-title": "Protein arginine deiminase 4 inhibition is sufficient for the amelioration of collagen-induced arthritis",
"author": "Willis",
"doi-asserted-by": "crossref",
"first-page": "263",
"journal-title": "Clin. Exp. Immunol.",
"key": "10.1016/j.isci.2026.115038_bib40",
"volume": "188",
"year": "2017"
},
{
"article-title": "Neutrophil extracellular traps in COVID-19",
"author": "Zuo",
"journal-title": "JCI Insight",
"key": "10.1016/j.isci.2026.115038_bib41",
"volume": "5",
"year": "2020"
},
{
"DOI": "10.3389/fcimb.2022.910908",
"article-title": "Impact of Neutrophil Extracellular Traps on Thrombosis Formation: New Findings and Future Perspective",
"author": "Zhou",
"doi-asserted-by": "crossref",
"first-page": "910908",
"journal-title": "Front. Cell. Infect. Microbiol.",
"key": "10.1016/j.isci.2026.115038_bib42",
"volume": "12",
"year": "2022"
},
{
"DOI": "10.1084/jem.20201129",
"article-title": "SARS-CoV-2 triggered neutrophil extracellular traps (NETs) mediate COVID-19 pathology",
"author": "Veras",
"doi-asserted-by": "crossref",
"journal-title": "J. Exp. Med.",
"key": "10.1016/j.isci.2026.115038_bib43",
"volume": "217",
"year": "2020"
},
{
"DOI": "10.1016/j.isci.2020.101947",
"article-title": "Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections",
"author": "Thair",
"doi-asserted-by": "crossref",
"journal-title": "iScience",
"key": "10.1016/j.isci.2026.115038_bib44",
"volume": "24",
"year": "2021"
},
{
"DOI": "10.1038/s41556-021-00796-6",
"article-title": "A single-cell transcriptomic landscape of the lungs of patients with COVID-19",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "1314",
"journal-title": "Nat. Cell Biol.",
"key": "10.1016/j.isci.2026.115038_bib45",
"volume": "23",
"year": "2021"
},
{
"DOI": "10.1038/s41586-021-03570-8",
"article-title": "COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets",
"author": "Delorey",
"doi-asserted-by": "crossref",
"first-page": "107",
"journal-title": "Nature",
"key": "10.1016/j.isci.2026.115038_bib46",
"volume": "595",
"year": "2021"
},
{
"DOI": "10.1093/jmcb/mjae004",
"article-title": "Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern",
"author": "Frasson",
"doi-asserted-by": "crossref",
"first-page": "mjae004",
"journal-title": "J. Mol. Cell Biol.",
"key": "10.1016/j.isci.2026.115038_bib47",
"volume": "16",
"year": "2024"
},
{
"DOI": "10.1002/jnr.22255",
"article-title": "Developmental and age-related changes of peptidylarginine deiminase 2 in the mouse brain",
"author": "Shimada",
"doi-asserted-by": "crossref",
"first-page": "798",
"journal-title": "J. Neurosci. Res.",
"key": "10.1016/j.isci.2026.115038_bib48",
"volume": "88",
"year": "2010"
},
{
"DOI": "10.1083/jcb.153.6.1301",
"article-title": "SERCA1 truncated proteins unable to pump calcium reduce the endoplasmic reticulum calcium concentration and induce apoptosis",
"author": "Chami",
"doi-asserted-by": "crossref",
"first-page": "1301",
"journal-title": "J. Cell Biol.",
"key": "10.1016/j.isci.2026.115038_bib49",
"volume": "153",
"year": "2001"
},
{
"DOI": "10.1016/j.isci.2021.102420",
"article-title": "Cell-type-resolved quantitative proteomics map of interferon response against SARS-CoV-2",
"author": "Saccon",
"doi-asserted-by": "crossref",
"journal-title": "iScience",
"key": "10.1016/j.isci.2026.115038_bib50",
"volume": "24",
"year": "2021"
},
{
"DOI": "10.1016/j.cell.2020.02.052",
"article-title": "SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor",
"author": "Hoffmann",
"doi-asserted-by": "crossref",
"first-page": "271",
"journal-title": "Cell",
"key": "10.1016/j.isci.2026.115038_bib51",
"volume": "181",
"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": "crossref",
"first-page": "475",
"journal-title": "Cell Host Microbe",
"key": "10.1016/j.isci.2026.115038_bib52",
"volume": "28",
"year": "2020"
},
{
"DOI": "10.1136/annrheumdis-2014-205365",
"article-title": "Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice",
"author": "Knight",
"doi-asserted-by": "crossref",
"first-page": "2199",
"journal-title": "Ann. Rheum. Dis.",
"key": "10.1016/j.isci.2026.115038_bib53",
"volume": "74",
"year": "2015"
},
{
"DOI": "10.1084/jem.20202135",
"article-title": "Neuroinvasion of SARS-CoV-2 in human and mouse brain",
"author": "Song",
"doi-asserted-by": "crossref",
"journal-title": "J. Exp. Med.",
"key": "10.1016/j.isci.2026.115038_bib54",
"volume": "218",
"year": "2021"
},
{
"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": "crossref",
"journal-title": "Commun. Biol.",
"key": "10.1016/j.isci.2026.115038_bib55",
"volume": "5",
"year": "2022"
},
{
"DOI": "10.1038/s41413-022-00211-2",
"article-title": "FABP4 secreted by M1-polarized macrophages promotes synovitis and angiogenesis to exacerbate rheumatoid arthritis",
"author": "Guo",
"doi-asserted-by": "crossref",
"first-page": "45",
"journal-title": "Bone Res.",
"key": "10.1016/j.isci.2026.115038_bib56",
"volume": "10",
"year": "2022"
},
{
"DOI": "10.1002/art.40066",
"article-title": "Anti-Citrullinated Protein Antibodies Are Associated With Neutrophil Extracellular Traps in the Sputum in Relatives of Rheumatoid Arthritis Patients",
"author": "Demoruelle",
"doi-asserted-by": "crossref",
"first-page": "1165",
"journal-title": "Arthritis Rheumatol.",
"key": "10.1016/j.isci.2026.115038_bib57",
"volume": "69",
"year": "2017"
},
{
"DOI": "10.1007/s11010-022-04591-1",
"article-title": "The emerging importance of immunophilins in fibrosis development",
"author": "Alqudah",
"doi-asserted-by": "crossref",
"first-page": "1281",
"journal-title": "Mol. Cell. Biochem.",
"key": "10.1016/j.isci.2026.115038_bib58",
"volume": "478",
"year": "2023"
},
{
"DOI": "10.1186/s12985-022-01802-5",
"article-title": "Replication kinetics and infectivity of SARS-CoV-2 variants of concern in common cell culture models",
"author": "Mautner",
"doi-asserted-by": "crossref",
"first-page": "76",
"journal-title": "Virol. J.",
"key": "10.1016/j.isci.2026.115038_bib59",
"volume": "19",
"year": "2022"
},
{
"DOI": "10.1128/mbio.03129-23",
"article-title": "Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating",
"author": "Tanneti",
"doi-asserted-by": "crossref",
"first-page": "e0312923",
"journal-title": "mBio",
"key": "10.1016/j.isci.2026.115038_bib60",
"volume": "15",
"year": "2024"
},
{
"DOI": "10.1074/mcp.RA118.000696",
"article-title": "Mining the human tissue proteome for protein citrullination",
"author": "Lee",
"doi-asserted-by": "crossref",
"first-page": "1378",
"journal-title": "Mol. Cell. Proteomics",
"key": "10.1016/j.isci.2026.115038_bib61",
"volume": "17",
"year": "2018"
},
{
"DOI": "10.1007/s11064-016-1920-2",
"article-title": "Myelin Basic Protein Citrullination in Multiple Sclerosis: A Potential Therapeutic Target for the Pathology",
"author": "Yang",
"doi-asserted-by": "crossref",
"first-page": "1845",
"journal-title": "Neurochem. Res.",
"key": "10.1016/j.isci.2026.115038_bib62",
"volume": "41",
"year": "2016"
},
{
"DOI": "10.1038/s41586-019-1404-z",
"article-title": "Neuronal vulnerability and multilineage diversity in multiple sclerosis",
"author": "Schirmer",
"doi-asserted-by": "crossref",
"first-page": "75",
"journal-title": "Nature",
"key": "10.1016/j.isci.2026.115038_bib63",
"volume": "573",
"year": "2019"
},
{
"DOI": "10.3390/cells11020253",
"article-title": "Calcium Signals during SARS-CoV-2 Infection: Assessing the Potential of Emerging Therapies",
"author": "Berlansky",
"doi-asserted-by": "crossref",
"journal-title": "Cells",
"key": "10.1016/j.isci.2026.115038_bib64",
"volume": "11",
"year": "2022"
},
{
"DOI": "10.1038/s41419-023-05817-w",
"article-title": "Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M",
"author": "Poggio",
"doi-asserted-by": "crossref",
"journal-title": "Cell Death Dis.",
"key": "10.1016/j.isci.2026.115038_bib65",
"volume": "14",
"year": "2023"
},
{
"DOI": "10.1038/s44319-024-00164-z",
"article-title": "Targeting ATP2B1 impairs PI3K/Akt/FOXO signaling and reduces SARS-COV-2 infection and replication",
"author": "de Antonellis",
"doi-asserted-by": "crossref",
"first-page": "2974",
"journal-title": "EMBO Rep.",
"key": "10.1016/j.isci.2026.115038_bib66",
"volume": "25",
"year": "2024"
},
{
"DOI": "10.1155/2019/7592851",
"article-title": "An overview of the intrinsic role of citrullination in autoimmune disorders",
"author": "Alghamdi",
"doi-asserted-by": "crossref",
"journal-title": "J. Immunol. Res.",
"key": "10.1016/j.isci.2026.115038_bib67",
"volume": "2019",
"year": "2019"
},
{
"DOI": "10.1016/j.heliyon.2024.e27997",
"article-title": "Association of PADI2 and PADI4 polymorphisms in COVID-19 host severity and non-survival",
"author": "Gutiérrez-Pérez",
"doi-asserted-by": "crossref",
"journal-title": "Heliyon",
"key": "10.1016/j.isci.2026.115038_bib68",
"volume": "10",
"year": "2024"
},
{
"DOI": "10.1016/j.cca.2025.120180",
"article-title": "Circulating levels of PADs and citrullinated histone H3 in SARS-CoV-2 infection: Influence of genetic polymorphisms",
"author": "Adriana Gutiérrez-Pérez",
"doi-asserted-by": "crossref",
"journal-title": "Clin. Chim. Acta",
"key": "10.1016/j.isci.2026.115038_bib69",
"volume": "569",
"year": "2025"
},
{
"DOI": "10.1016/j.mucimm.2025.04.006",
"article-title": "PAD4 inhibition impacts immune responses in SARS-CoV-2 infection",
"author": "Bonilha",
"doi-asserted-by": "crossref",
"first-page": "861",
"journal-title": "Mucosal Immunol.",
"key": "10.1016/j.isci.2026.115038_bib70",
"volume": "18",
"year": "2025"
},
{
"DOI": "10.1371/journal.ppat.1009195",
"article-title": "K18-hACE2 mice develop respiratory disease resembling severe COVID-19",
"author": "Yinda",
"doi-asserted-by": "crossref",
"journal-title": "PLoS Pathog.",
"key": "10.1016/j.isci.2026.115038_bib71",
"volume": "17",
"year": "2021"
},
{
"DOI": "10.1007/s13365-021-01029-0",
"article-title": "Longitudinal, virological, and serological assessment of hospitalized COVID-19 patients",
"author": "Signorini",
"doi-asserted-by": "crossref",
"first-page": "113",
"journal-title": "J. Neurovirol.",
"key": "10.1016/j.isci.2026.115038_bib72",
"volume": "28",
"year": "2022"
},
{
"DOI": "10.1186/s13046-023-02628-x",
"article-title": "Guadecitabine increases response to combined anti-CTLA-4 and anti-PD-1 treatment in mouse melanoma in vivo by controlling T-cells, myeloid derived suppressor and NK cells",
"author": "Amaro",
"doi-asserted-by": "crossref",
"first-page": "67",
"journal-title": "J. Exp. Clin. Cancer Res.",
"key": "10.1016/j.isci.2026.115038_bib73",
"volume": "42",
"year": "2023"
},
{
"DOI": "10.1093/nar/gkae1011",
"article-title": "The PRIDE database at 20 years: 2025 update",
"author": "Perez-Riverol",
"doi-asserted-by": "crossref",
"first-page": "D543",
"journal-title": "Nucleic Acids Res.",
"key": "10.1016/j.isci.2026.115038_bib74",
"volume": "53",
"year": "2025"
},
{
"article-title": "Empirical statistical model to estimate the accuracy of protein identifications made by MS/MS and database search",
"author": "Keller",
"first-page": "37",
"key": "10.1016/j.isci.2026.115038_bib75",
"volume": "74",
"year": "2002"
},
{
"DOI": "10.1021/ac0341261",
"article-title": "A statistical model for identifying proteins by tandem mass spectrometry",
"author": "Nesvizhskii",
"doi-asserted-by": "crossref",
"first-page": "4646",
"journal-title": "Anal. Chem.",
"key": "10.1016/j.isci.2026.115038_bib76",
"volume": "75",
"year": "2003"
},
{
"DOI": "10.1186/1471-2164-6-145",
"article-title": "i-Tracker: For quantitative proteomics using iTRAQ™",
"author": "Shadforth",
"doi-asserted-by": "crossref",
"first-page": "1",
"journal-title": "BMC Genom.",
"key": "10.1016/j.isci.2026.115038_bib77",
"volume": "6",
"year": "2005"
},
{
"DOI": "10.1021/pr8010099",
"article-title": "Statistical design of quantitative mass spectrometry-based proteomic experiments",
"author": "Oberg",
"doi-asserted-by": "crossref",
"first-page": "2144",
"journal-title": "J. Proteome Res.",
"key": "10.1016/j.isci.2026.115038_bib78",
"volume": "8",
"year": "2009"
}
],
"reference-count": 77,
"references-count": 77,
"relation": {},
"resource": {
"primary": {
"URL": "https://linkinghub.elsevier.com/retrieve/pii/S258900422600413X"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response",
"type": "journal-article",
"update-policy": "https://doi.org/10.1016/elsevier_cm_policy",
"volume": "29"
}