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In SARS-CoV-2 delta variants, Spike-P681R and D950N promote membrane fusion, Spike-P681R enhances spike cleavage, but neither substitution affects pathogenicity in hamsters.
- Source :
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EBioMedicine [EBioMedicine] 2023 May; Vol. 91, pp. 104561. Date of Electronic Publication: 2023 Apr 10. - Publication Year :
- 2023
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Abstract
- Background: The SARS-CoV-2 delta (B.1.617.2 lineage) variant was first identified at the end of 2020 and possessed two unique amino acid substitutions in its spike protein: S-P681R, at the S1/S2 cleavage site, and S-D950N, in the HR1 of the S2 subunit. However, the roles of these substitutions in virus phenotypes have not been fully characterized.<br />Methods: We used reverse genetics to generate Wuhan-D614G viruses with these substitutions and delta viruses lacking these substitutions and explored how these changes affected their viral characteristics in vitro and in vivo.<br />Findings: S-P681R enhanced spike cleavage and membrane fusion, whereas S-D950N slightly promoted membrane fusion. Although S-681R reduced the virus replicative ability especially in VeroE6 cells, neither substitution affected virus replication in Calu-3 cells and hamsters. The pathogenicity of all recombinant viruses tested in hamsters was slightly but not significantly affected.<br />Interpretation: Our observations suggest that the S-P681R and S-D950N substitutions alone do not increase virus pathogenicity, despite of their enhancement of spike cleavage or fusogenicity.<br />Funding: A full list of funding bodies that contributed to this study can be found under Acknowledgments.<br />Competing Interests: Declaration of interests Y.K. has received collaborative research funds from the following companies. For antiviral studies; FUJIFILM Toyama Chemical Co. LTD (various viruses), Shionogi &; Co. LTD (influenza viruses). For vaccine and other studies; Daiichi Sankyo Pharmaceutical, Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Fuji Rebio, Tauns Laboratories, Inc., Matsubara Co. LTD. As the Flagship Center of the Japan Initiative for World-leading Vaccine Research and Development Centers, we plan to initiate collaborative research related to vaccine development with the following companies: Shionogi &Co. LTD, Daiichi Sankyo Pharmaceutical, KM Biologics, Cytiva, Sysmex Corporation, NEC.<br /> (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cricetinae
Virulence genetics
Membrane Fusion
SARS-CoV-2
COVID-19
Subjects
Details
- Language :
- English
- ISSN :
- 2352-3964
- Volume :
- 91
- Database :
- MEDLINE
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- 37043872
- Full Text :
- https://doi.org/10.1016/j.ebiom.2023.104561