Engineered ACE2-Fc counters murine lethal SARS-CoV-2 infection through direct neutralization and Fc-effector activities.


Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
24 Nov 2021
Historique:
entrez: 30 11 2021
pubmed: 1 12 2021
medline: 1 12 2021
Statut: epublish

Résumé

Soluble Angiotensin-Converting Enzyme 2 (ACE2) constitutes an attractive antiviral capable of targeting a wide range of coronaviruses utilizing ACE2 as their receptor. Here, using structure-guided approaches, we developed divalent ACE2 molecules by grafting the extracellular ACE2-domain onto a human IgG1 or IgG3 (ACE2-Fc). These ACE2-Fcs harbor structurally validated mutations that enhance spike (S) binding and remove angiotensin enzymatic activity. The lead variant bound tightly to S, mediated

Identifiants

pubmed: 34845451
doi: 10.1101/2021.11.24.469776
pmc: PMC8629194
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI163395
Pays : United States

Commentaires et corrections

Type : UpdateIn

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Auteurs

Yaozong Chen (Y)

Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.
equal contribution.

Lulu Sun (L)

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
equal contribution.

Irfan Ullah (I)

Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
equal contribution.

Guillaume Beaudoin-Bussières (G)

Centre de recherche du CHUM. Montreal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.

Sai Priya Anand (SP)

Centre de recherche du CHUM. Montreal, QC H2X 0A9, Canada.
Department of Microbiology and Immunology, McGill, QC, Canada.

Andrew P Hederman (AP)

Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.

William D Tolbert (WD)

Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.

Rebekah Sherburn (R)

Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.

Dung N Nguyen (DN)

Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.

Lorie Marchitto (L)

Centre de recherche du CHUM. Montreal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.

Shilei Ding (S)

Centre de recherche du CHUM. Montreal, QC H2X 0A9, Canada.

Di Wu (D)

Biophysics Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892.

Yuhong Luo (Y)

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.

Suneetha Gottumukkala (S)

Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.

Sean Moran (S)

Biomedical Instrumentation Center, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.

Priti Kumar (P)

Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.

Grzegorz Piszczek (G)

Biophysics Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892.

Walther Mothes (W)

Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.

Margaret E Ackerman (ME)

Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.

Andrés Finzi (A)

Centre de recherche du CHUM. Montreal, QC H2X 0A9, Canada.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Department of Microbiology and Immunology, McGill, QC, Canada.

Pradeep D Uchil (PD)

Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.

Frank J Gonzalez (FJ)

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.

Marzena Pazgier (M)

Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.

Classifications MeSH