A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro.

Antibodies, Monoclonal COVID-19 Enterotoxins Humans SARS-CoV-2 Spike Glycoprotein, Coronavirus Superantigens Systemic Inflammatory Response Syndrome
6D3 COVID-19 MIS-C TMPRSS2 cytokine storm furin-cleavage site neutralizing antibodies staphylococcal enterotoxin B superantigen viral entry

Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
02 09 2021
Historique:
received: 29 01 2021
revised: 28 02 2021
accepted: 08 04 2021
pubmed: 1 5 2021
medline: 10 9 2021
entrez: 30 4 2021
Statut: ppublish

Résumé

We recently discovered a superantigen-like motif sequentially and structurally similar to a staphylococcal enterotoxin B (SEB) segment, near the S1/S2 cleavage site of the SARS-CoV-2 spike protein, which might explain the multisystem inflammatory syndrome (MIS-C) observed in children and the cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif at its polybasic (PRRA) insert to inhibit infection in live virus assays. The overlap between the superantigenic site of the spike and its proteolytic cleavage site suggests that the mAb prevents viral entry by interfering with the proteolytic activity of cell proteases (furin and TMPRSS2). The high affinity of 6D3 for this site originates from a polyacidic segment at its heavy chain CDR2. The study points to the potential utility of 6D3 for possibly treating COVID-19, MIS-C, or common colds caused by human coronaviruses that also possess a furin-like cleavage site.

Identifiants

DOI: 10.1016/j.str.2021.04.005 PMID: 33930306 PMC: PMC8082696
pubmed: 33930306
pii: S0969-2126(21)00121-0
doi: 10.1016/j.str.2021.04.005
pmc: PMC8082696
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Enterotoxins 0
Spike Glycoprotein, Coronavirus 0
Superantigens 0
spike protein, SARS-CoV-2 0
enterotoxin B, staphylococcal 39424-53-8

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Comment

Langues

eng

Sous-ensembles de citation

IM

Pagination

951-962.e3

Subventions

Organisme : BLRD VA
ID : I01 BX003741
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103712
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI072726
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127704
Pays : United States

Commentaires et corrections

Type : CommentOn
Type : UpdateOf

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Mary Hongying Cheng (MH)

Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Rebecca A Porritt (RA)

Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Magali Noval Rivas (MN)

Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

James M Krieger (JM)

Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Asli Beyza Ozdemir (AB)

Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Gustavo Garcia (G)

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Vaithilingaraja Arumugaswami (V)

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Bettina C Fries (BC)

Department of Medicine, Stony Brook University Hospital, Stony Brook, New York, NY 11794, USA; Northport VA Medical Center, Northport, NY 11768, USA.

Moshe Arditi (M)

Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: moshe.arditi@cshs.org.

Ivet Bahar (I)

Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: bahar@pitt.edu.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › A monoclonal antibody against staphylococcal...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › A monoclonal antibody against staphylococcal...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Entérotoxines › A monoclonal antibody against staphylococcal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A monoclonal antibody against staphylococcal...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › A monoclonal antibody against staphylococcal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Protéines de fusion virale › Glycoprotéine de spicule des coronavirus › A monoclonal antibody against staphylococcal...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Superantigènes › A monoclonal antibody against staphylococcal...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Choc › Syndrome de réponse inflammatoire généralisée › A monoclonal antibody against staphylococcal...