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Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant.
Cell Rep. 2022 05 17; 39(7):110829.CR

Abstract

We report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement during the coronavirus disease 2019 (COVID-19) pandemic. Delta SARS-CoV-2 efficiently outcompetes the Alpha variant in human lung epithelial cells and primary human airway tissues. The Delta spike mutation P681R is located at a furin cleavage site that separates the spike 1 (S1) and S2 subunits. Reverting the P681R mutation to wild-type P681 significantly reduces the replication of the Delta variant to a level lower than the Alpha variant. Mechanistically, the Delta P681R mutation enhances the cleavage of the full-length spike to S1 and S2, which could improve cell-surface-mediated virus entry. In contrast, the Alpha spike also has a mutation at the same amino acid (P681H), but the cleavage of the Alpha spike is reduced compared with the Delta spike. Our results suggest P681R as a key mutation in enhancing Delta-variant replication via increased S1/S2 cleavage.

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Authors+Show Affiliations

Liu Y
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
Liu J
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Johnson BA
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Xia H
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
Ku Z
Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Schindewolf C
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Widen SG
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
An Z
Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Weaver SC
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Menachery VD
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Xie X
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: xuxie@utmb.edu.
Shi PY
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: peshi@utmb.edu.

MeSH

COVID-19HumansMutationSARS-CoV-2Spike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

35550680

Citation

Liu, Yang, et al. "Delta Spike P681R Mutation Enhances SARS-CoV-2 Fitness Over Alpha Variant." Cell Reports, vol. 39, no. 7, 2022, p. 110829.
Liu Y, Liu J, Johnson BA, et al. Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant. Cell Rep. 2022;39(7):110829.
Liu, Y., Liu, J., Johnson, B. A., Xia, H., Ku, Z., Schindewolf, C., Widen, S. G., An, Z., Weaver, S. C., Menachery, V. D., Xie, X., & Shi, P. Y. (2022). Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant. Cell Reports, 39(7), 110829. https://doi.org/10.1016/j.celrep.2022.110829
Liu Y, et al. Delta Spike P681R Mutation Enhances SARS-CoV-2 Fitness Over Alpha Variant. Cell Rep. 2022 05 17;39(7):110829. PubMed PMID: 35550680.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant. AU - Liu,Yang, AU - Liu,Jianying, AU - Johnson,Bryan A, AU - Xia,Hongjie, AU - Ku,Zhiqiang, AU - Schindewolf,Craig, AU - Widen,Steven G, AU - An,Zhiqiang, AU - Weaver,Scott C, AU - Menachery,Vineet D, AU - Xie,Xuping, AU - Shi,Pei-Yong, Y1 - 2022/04/29/ PY - 2022/03/03/received PY - 2022/03/28/revised PY - 2022/04/26/accepted PY - 2022/5/14/pubmed PY - 2022/5/21/medline PY - 2022/5/13/entrez KW - CP: Microbiology KW - Delta variant KW - S1/S2 cleavage KW - SARS-CoV-2 KW - fitness KW - human airway culture KW - spike P681R KW - viral entry SP - 110829 EP - 110829 JF - Cell reports JO - Cell Rep VL - 39 IS - 7 N2 - We report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement during the coronavirus disease 2019 (COVID-19) pandemic. Delta SARS-CoV-2 efficiently outcompetes the Alpha variant in human lung epithelial cells and primary human airway tissues. The Delta spike mutation P681R is located at a furin cleavage site that separates the spike 1 (S1) and S2 subunits. Reverting the P681R mutation to wild-type P681 significantly reduces the replication of the Delta variant to a level lower than the Alpha variant. Mechanistically, the Delta P681R mutation enhances the cleavage of the full-length spike to S1 and S2, which could improve cell-surface-mediated virus entry. In contrast, the Alpha spike also has a mutation at the same amino acid (P681H), but the cleavage of the Alpha spike is reduced compared with the Delta spike. Our results suggest P681R as a key mutation in enhancing Delta-variant replication via increased S1/S2 cleavage. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/35550680/Delta_spike_P681R_mutation_enhances_SARS_CoV_2_fitness_over_Alpha_variant_ DB - PRIME DP - Unbound Medicine ER -