Functional evaluation of the P681H mutation on the proteolytic activation the SARS-CoV-2 variant B.1.1.7 (Alpha) spike.

Autor:	Lubinski B; Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, 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, 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, Ithaca, NY, 14853, USA., Whittaker GR; Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.; Master of Public Health Program, Cornell University, Ithaca, NY, 14853, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2021 Nov 01. Date of Electronic Publication: 2021 Nov 01.
DOI:	10.1101/2021.04.06.438731
Abstrakt:	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 (VOC) first identified in the UK 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 while the B.1.1.7 P681H mutation may slightly increase S1/S2 cleavage this does not significantly impact viral entry or cell-cell spread. Competing Interests: Declaration of Interests The authors manifest no conflict of interest.
Databáze:	MEDLINE
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