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Functional evaluation of the P681H mutation on the proteolytic activation of the SARS-CoV-2 variant B.1.1.7 (Alpha) spike.
Lubinski, Bailey; Fernandes, Maureen H V; Frazier, Laura; Tang, Tiffany; Daniel, Susan; Diel, Diego G; Jaimes, Javier A; Whittaker, Gary R.
  • Lubinski B; Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, 618 Tower Road, Ithaca, NY 14853, USA.
  • Fernandes MHV; Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
  • Frazier L; Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, 618 Tower Road, Ithaca, NY 14853, USA.
  • Tang T; Robert Frederick Smith School of Chemical & Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
  • Daniel S; Robert Frederick Smith School of Chemical & Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
  • Diel DG; Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
  • Jaimes JA; Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, 618 Tower Road, Ithaca, NY 14853, USA.
  • Whittaker GR; Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, 618 Tower Road, Ithaca, NY 14853, USA.
iScience ; 25(1): 103589, 2022 Jan 21.
Article in English | MEDLINE | ID: covidwho-1882120
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent causing the COVID-19 pandemic. SARS-CoV-2 B.1.1.7 (Alpha), a WHO variant of concern first identified in the United Kingdom in late 2020, contains several mutations including P681H in the spike S1/S2 cleavage site, which is predicted to increase cleavage by furin, potentially impacting the viral cell entry. Here, we studied the role of the P681H mutation in B.1.1.7 cell entry. We performed assays using fluorogenic peptides mimicking the Wuhan-Hu-1 and B.1.1.7 S1/S2 sequence and observed no significant difference in furin cleavage. Functional assays using pseudoparticles harboring SARS-CoV-2 spikes and cell-to-cell fusion assays demonstrated no differences between Wuhan-Hu-1, B.1.1.7, or a P681H point mutant. Likewise, we observed no differences in viral growth between USA-WA1/2020 and a B.1.1.7 isolate in cell culture. Our findings suggest that, although the B.1.1.7 P681H mutation may slightly increase S1/S2 cleavage, this does not significantly impact viral entry or cell-cell spread.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2021.103589

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2021.103589