ArticleCell death & disease2021
Inhibition of HECT E3 ligases as potential therapy for COVID-19.
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Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
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Who cites it
41 citing papers in PubMed, 54 citations in OpenAlex.
- Therapeutic Efficacy of Indole-3-Carbinol Against SARS-CoV-2-Induced Acute Respiratory Distress Syndrome: A Dual Antiviral and Anti-Inflammatory Approach in a Golden Syrian Hamster Model.Journal of cellular and molecular medicine · 2026Article
- Article
- E3 ubiquitin ligase NEDD4 inhibits PEDV infection through ubiquitination and degradation of the viral primase NSP8.Journal of virology · 2026Article
- WWP1 gain-of-function drives developmental anoikis through TGFβ pathway during neurodevelopment.Cell death discovery · 2026Article
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- Therapeutic potential of nutritional aryl hydrocarbon receptor ligands for respiratory syncytial virus infection: a mini review.Frontiers in microbiology · 2026Review
- SMURF2 inhibits autophagic control ofbioRxiv : the preprint server for biology · 2025Article
- Identification and validation of the cellular senescence-associated molecular pattern and diagnostic markers for osteoporosis.BMC medical genomics · 2025Article
- [WW domain-containing ubiquitin E3 ligase 1 regulates immune infiltration in tumor microenvironment of ovarian cancer].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- 3,3'-Diindolylmethane (DIM): A Molecular Scaffold for Inhibition of WWP1 and WWP2, Members of the NEDD4 Family HECT E3 Ligases.ACS omega · 2025Article
- Optimizing the Antimicrobial Effects by using Natural Compounds in COVID-19 Management.Current medicinal chemistry · 2025Review
- Expanding the inhibitor space of the WWP1 and WWP2 HECT E3 ligases.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Human E3 ubiquitin ligases: accelerators and brakes for SARS-CoV-2 infection.Biochemical Society transactions · 2024Review
- E3 Ubiquitin Ligase Smurf1 Regulates the Inflammatory Response in Macrophages and Attenuates Hepatic Damage during Betacoronavirus Infection.Pathogens (Basel, Switzerland) · 2024Article
- Protective Effect of Indole-3-Aldehyde in Murine COVID-19-Associated Pulmonary Aspergillosis.Journal of fungi (Basel, Switzerland) · 2024Article
- Multiple E3 ligases act as antiviral factors against SARS-CoV-2 via inducing the ubiquitination and degradation of ORF9b.Journal of virology · 2024Article
- 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.International journal of molecular sciences · 2024Article
- COVID-19 plasma induces subcellular remodelling within the pulmonary microvascular endothelium.Vascular pharmacology · 2024Article
- WWP1 E3 ligase at the crossroads of health and disease.Cell death & disease · 2023Review
- E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation.Viruses · 2023Review
Corrections and comments
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Authors and funding
43 authors at 14 institutions in 4 countries.
Giuseppe NovelliDepartment of Biomedicine and Prevention, Tor Vergata University of Rome, 00133, Rome, Italy. novelli@med.uniroma2.it.ORCID http://orcid.org/0000-0002-7781-602X
Jing LiuDepartment of Pathology, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, MA, 02215, USA.
Michela BiancolellaDepartment of Biology, Tor Vergata University, 00133, Rome, Italy.
Tonino AlonziTranslational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases Lazzaro Spallanzani - IRCCS, 00149, Rome, Italy.
Antonio NovelliLaboratory of Medical Genetics, IRCCS Bambino Gesù Children's Hospital, 00165, Rome, Italy.
J J PattenNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9770-7525
Dario CocciadiferroLaboratory of Medical Genetics, IRCCS Bambino Gesù Children's Hospital, 00165, Rome, Italy.
Emanuele AgoliniLaboratory of Medical Genetics, IRCCS Bambino Gesù Children's Hospital, 00165, Rome, Italy.ORCID http://orcid.org/0000-0001-6543-6225
Vito Luigi ColonaDepartment of Biomedicine and Prevention, Tor Vergata University of Rome, 00133, Rome, Italy.ORCID http://orcid.org/0000-0002-9660-7397
Barbara RizzacasaDepartment of Biomedicine and Prevention, Tor Vergata University of Rome, 00133, Rome, Italy.ORCID http://orcid.org/0000-0002-4820-4403
Rosalinda GianniniDepartment of Biomedicine and Prevention, Tor Vergata University of Rome, 00133, Rome, Italy.
Benedetta BigioSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, 10065, USA.
Delia GolettiTranslational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases Lazzaro Spallanzani - IRCCS, 00149, Rome, Italy.
Maria Rosaria CapobianchiLaboratory of Virology, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases Lazzaro Spallanzani - IRCCS, 00149, Rome, Italy.
Sandro GrelliDepartment of Experimental Medicine, Tor Vergata University of Rome, 00133, Rome, Italy.
Justin MannHistoWiz Inc, Brooklyn, NY, 11226, USA.
Trevor D McKeeHistoWiz Inc, Brooklyn, NY, 11226, USA.
Ke ChengHistoWiz Inc, Brooklyn, NY, 11226, USA.
Fatima AmanatDepartment of Microbiology, Icahn school of Medicine at Mount Sinai, New York, NY, 10029, USA.
Florian KrammerDepartment of Microbiology, Icahn school of Medicine at Mount Sinai, New York, NY, 10029, USA.
Andrea GuarracinoDepartment of Biology, Tor Vergata University, 00133, Rome, Italy.ORCID http://orcid.org/0000-0001-9744-131X
Gerardo PepeDepartment of Biology, Tor Vergata University, 00133, Rome, Italy.ORCID http://orcid.org/0000-0001-5308-2765
Carlo TominoSan Raffaele University of Rome, 00166, Rome, Italy.
Yacine Tandjaoui-LambiotteIntensive Care Unit, Avicenne Hospital, APHP, Bobigny, France.
Yurdagul UzunhanPneumology Department, Reference Center for Rare Pulmonary Diseases, Hôpital Avicenne, APHP, Bobigny; INSERM UMR1272, Université Paris 13, Bobigny, France.
Sarah TubianaHôpital Bichat Claude Bernard, APHP, Paris, France.
Jade GhosnInfection, Antimicrobials, Modelling, Evolution (IAME), INSERM, UMRS1137, University of Paris, Paris, France.
COVID Human Genetic Effort
French COVID Cohort Study Group
CoV-Contact Cohort
Luigi D NotarangeloLaboratory of Clinical Immunology, NIAID, NIH, Bethesda, MD, USA.
Helen C SuLaboratory of Clinical Immunology, NIAID, NIH, Bethesda, MD, USA.
Laurent AbelSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, 10065, USA.
Aurélie CobatSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, 10065, USA.
Gai ElhananCenter for Genomic Medicine, Desert Research Institute, Reno, NV, 89502, USA.
Joseph J GrzymskiCenter for Genomic Medicine, Desert Research Institute, Reno, NV, 89502, USA.
Andrea LatiniDepartment of Biomedicine and Prevention, Tor Vergata University of Rome, 00133, Rome, Italy.
Sachdev S SidhuThe Donnelly Centre, University of Toronto, Toronto, Ontario, Canada, M5S 3E1 416-946-0863.
Suresh JainVirna Therapeutics, West Roxbury, MA, USA.
Robert A DaveyDepartment of Microbiology Boston University, National Emerging Infectious Diseases Laboratories, Boston, MA, 02118, USA.
Jean-Laurent CasanovaSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, 10065, USA.
Wenyi WeiDepartment of Pathology, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, MA, 02215, USA.
Pier Paolo PandolfiDepartment of Pathology, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, MA, 02215, USA. pierpaolo.pandolfiderinaldis@renown.org.
University of Rome Tor Vergata · ITInserm · FRBeth Israel Deaconess Medical Center · USNational Institutes of Health · USBambino Gesù Children's Hospital · ITBoston University · USIstituto Nazionale per le Malattie Infettive Lazzaro Spallanzani · ITIcahn School of Medicine at Mount Sinai · USUniversité Claude Bernard Lyon 1 · FRDesert Research Institute · USHoward Hughes Medical Institute · USRockefeller University · USSan Raffaele University of Rome · ITUniversity of Toronto · CA
Funding
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MYale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8MHost factors contributing to susceptibility to COVID-19 diseaseZIAAI001265 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2020 to 2025
$9.5MMonogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19R01AI088364 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Jean-Laurent Casanova, Shen-Ying Zhang · 2010 to 2026
$8.7MNHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9MCharacterization of host immune responses to SARS-CoV-2ZIAAI001270 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NOTARANGELO, LUIGI · 2020 to 2025
$1.2MAgence Nationale de la Recherche (French National Research Agency) ANR-10-IAHU-01Agence Nationale de la Recherche (French National Research Agency) ANR-10-LABX-62-IBEIDHoward Hughes Medical InstituteNHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006504NIAID NIH HHS R01 AI088364
Abstract
SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we find that HECT family members are overexpressed in primary samples derived from COVID-19 infected patients and COVID-19 mouse models. Importantly, rare germline activating variants in the NEDD4 and WWP1 genes are associated with severe COVID-19 cases. Critically, I3C, a natural NEDD4 and WWP1 inhibitor from Brassicaceae, displays potent antiviral effects and inhibits viral egression. In conclusion, we identify the HECT family members of E3 ligases as likely novel biomarkers for COVID-19, as well as new potential targets of therapeutic strategy easily testable in clinical trials in view of the established well-tolerated nature of the Brassicaceae natural compounds.
Indexed as
COVID-19 Drug TreatmentAdultAgedAnimalsAntiviral AgentsChlorocebus aethiopsCOVID-19Endosomal Sorting Complexes Required for TransportFemaleHumansIndolesMaleMiceMice, Inbred BALB CMiddle AgedNedd4 Ubiquitin Protein LigasesAntiviral AgentsEndosomal Sorting Complexes Required for Transportindole-3-carbinolIndolesNedd4 Ubiquitin Protein LigasesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Ubiquitin-Protein LigasesWWP1 protein, human
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