Evidence map›Paper›PMID 41797904›Full record

ArticleiScience2026

Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response.

Selina Pasquero, Alessandro Penna, Lucia Signorini, Salvatore Villani, Francesca Gugliesi, Valeria Caneparo, Francesco Favero, Webb Camille, Robert M Green, Ilaria Frasson and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Selina PasqueroDepartment of Public Health and Pediatric Sciences, University of Turin - Medical School, Turin, Italy.
Alessandro PennaDepartment of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy.
Lucia SignoriniDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Salvatore VillaniDepartment of Pharmaceutical Sciences, University of Eastern Piedmont, Novara, Italy.
Francesca GugliesiDepartment of Public Health and Pediatric Sciences, University of Turin - Medical School, Turin, Italy.
Valeria CaneparoCAAD Center for Translational Research on Autoimmune and Allergic Disease, University of Eastern Piedmont, Novara Medical School, Novara, Italy.
Francesco FaveroCAAD Center for Translational Research on Autoimmune and Allergic Disease, University of Eastern Piedmont, Novara Medical School, Novara, Italy.
Webb CamilleDepartment of Biochemistry and Molecular Pharmacology, UMass Medical School, Worcester, MA, USA.
Robert M GreenDepartment of Biochemistry and Molecular Pharmacology, UMass Medical School, Worcester, MA, USA.
Ilaria FrassonDepartment of Molecular Medicine, University of Padua, Padua, Italy.
Anna TosiImmunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Beatrice GenovaImmunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Anna Dalla PietàDepartment of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy.
Ranieri VerinDepartment of Comparative Biomedicine and Food Science, University of Padua, Padua, Italy.
Sofia TomasoniDepartment of Comparative Biomedicine and Food Science, University of Padua, Padua, Italy.
Erika Del GrossoDepartment of Pharmaceutical Sciences, University of Eastern Piedmont, Novara, Italy.
Serena DelbueDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Sara N RichterDepartment of Molecular Medicine, University of Padua, Padua, Italy.
Paul R ThompsonDepartment of Biochemistry and Molecular Pharmacology, UMass Medical School, Worcester, MA, USA.
Antonio RosatoDepartment of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy.
Marco De AndreaDepartment of Public Health and Pediatric Sciences, University of Turin - Medical School, Turin, Italy.

Funding

Chemical probes to decipher PAD biologyR35GM118112 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Paul R Thompson · 2016 to 2026
$9.5M
NIGMS NIH HHS R35 GM118112
6 · The paper itself

Abstract

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 findings suggest that SARS-CoV-2 exploits PAD-mediated citrullination to enhance replication and inflammation. Thus, targeting PAD4 may represent a viable strategy to curb viral spread and mitigate COVID-19-associated hyperinflammation.

Indexed as

biological sciencesmicrobiologyNatural sciencesvirology

Identifiers

PMID41797904
PMCPMC12966709

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.