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A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding.
Immunol Lett. 2022 02; 242:1-7.IL

Abstract

SARS-CoV-2 harbors a unique S1/S2 furin cleavage site within its spike protein, which can be cleaved by furin and other proprotein convertases. Proteolytic activation of SARS-CoV-2 spike protein at the S1/S2 boundary facilitates interaction with host ACE2 receptor for cell entry. To address this, high titer antibody was generated against the SARS-CoV-2-specific furin motif. Using a series of innovative ELISA-based assays, this furin site blocking antibody displayed high sensitivity and specificity for the S1/S2 furin cleavage site, including with a P681R mutation, and demonstrated effective blockage of both enzyme-mediated cleavage and spike-ACE2 interaction. The results suggest that immunological blocking of the furin cleavage site may afford a suitable approach to stem proteolytic activation of SARS-CoV-2 spike protein and curtail viral infectivity.

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Authors+Show Affiliations

Spelios MG
EpiGentek Group Inc., 110 Bi County Boulevard, Suite 122, Farmingdale, NY, 11735, United States of America.
Capanelli JM
EpiGentek Group Inc., 110 Bi County Boulevard, Suite 122, Farmingdale, NY, 11735, United States of America.
Li AW
EpiGentek Group Inc., 110 Bi County Boulevard, Suite 122, Farmingdale, NY, 11735, United States of America. Electronic address: awli@epigentek.com.

MeSH

Amino Acid MotifsAngiotensin-Converting Enzyme 2Antibodies, ViralFurinHumansMutationNoseProprotein ConvertasesProtein BindingProteolysisSARS-CoV-2Spike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35007661

Citation

Spelios, Michael G., et al. "A Novel Antibody Against the Furin Cleavage Site of SARS-CoV-2 Spike Protein: Effects On Proteolytic Cleavage and ACE2 Binding." Immunology Letters, vol. 242, 2022, pp. 1-7.
Spelios MG, Capanelli JM, Li AW. A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding. Immunol Lett. 2022;242:1-7.
Spelios, M. G., Capanelli, J. M., & Li, A. W. (2022). A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding. Immunology Letters, 242, 1-7. https://doi.org/10.1016/j.imlet.2022.01.002
Spelios MG, Capanelli JM, Li AW. A Novel Antibody Against the Furin Cleavage Site of SARS-CoV-2 Spike Protein: Effects On Proteolytic Cleavage and ACE2 Binding. Immunol Lett. 2022;242:1-7. PubMed PMID: 35007661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding. AU - Spelios,Michael G, AU - Capanelli,Jeanne M, AU - Li,Adam W, Y1 - 2022/01/07/ PY - 2021/05/17/received PY - 2022/01/05/revised PY - 2022/01/06/accepted PY - 2022/1/11/pubmed PY - 2022/2/12/medline PY - 2022/1/10/entrez KW - ACE2 KW - COVID-19 KW - Furin KW - Furin site blocking antibody KW - Proprotein convertase KW - SARS-CoV-2 KW - Spike SP - 1 EP - 7 JF - Immunology letters JO - Immunol Lett VL - 242 N2 - SARS-CoV-2 harbors a unique S1/S2 furin cleavage site within its spike protein, which can be cleaved by furin and other proprotein convertases. Proteolytic activation of SARS-CoV-2 spike protein at the S1/S2 boundary facilitates interaction with host ACE2 receptor for cell entry. To address this, high titer antibody was generated against the SARS-CoV-2-specific furin motif. Using a series of innovative ELISA-based assays, this furin site blocking antibody displayed high sensitivity and specificity for the S1/S2 furin cleavage site, including with a P681R mutation, and demonstrated effective blockage of both enzyme-mediated cleavage and spike-ACE2 interaction. The results suggest that immunological blocking of the furin cleavage site may afford a suitable approach to stem proteolytic activation of SARS-CoV-2 spike protein and curtail viral infectivity. SN - 1879-0542 UR - https://www.unboundmedicine.com/medline/citation/35007661/A_novel_antibody_against_the_furin_cleavage_site_of_SARS_CoV_2_spike_protein:_Effects_on_proteolytic_cleavage_and_ACE2_binding_ DB - PRIME DP - Unbound Medicine ER -