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A second functional furin site in the SARS-CoV-2 spike protein

The ubiquitously-expressed proteolytic enzyme furin is closely related to the pathogenesis of SARS-CoV-2 and therefore represents a key target for antiviral therapy. Based on bioinformatic analysis and pseudovirus tests, we discovered a second functional furin site located in the spike protein. Furi...

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Autores principales: Zhang, Yue, Zhang, Li, Wu, Jiajing, Yu, Yuanling, Liu, Shuo, Li, Tao, Li, Qianqian, Ding, Ruxia, Wang, Haixin, Nie, Jianhui, Cui, Zhimin, Wang, Yulin, Huang, Weijin, Wang, Youchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741242/
https://www.ncbi.nlm.nih.gov/pubmed/34856891
http://dx.doi.org/10.1080/22221751.2021.2014284
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author Zhang, Yue
Zhang, Li
Wu, Jiajing
Yu, Yuanling
Liu, Shuo
Li, Tao
Li, Qianqian
Ding, Ruxia
Wang, Haixin
Nie, Jianhui
Cui, Zhimin
Wang, Yulin
Huang, Weijin
Wang, Youchun
author_facet Zhang, Yue
Zhang, Li
Wu, Jiajing
Yu, Yuanling
Liu, Shuo
Li, Tao
Li, Qianqian
Ding, Ruxia
Wang, Haixin
Nie, Jianhui
Cui, Zhimin
Wang, Yulin
Huang, Weijin
Wang, Youchun
author_sort Zhang, Yue
collection PubMed
description The ubiquitously-expressed proteolytic enzyme furin is closely related to the pathogenesis of SARS-CoV-2 and therefore represents a key target for antiviral therapy. Based on bioinformatic analysis and pseudovirus tests, we discovered a second functional furin site located in the spike protein. Furin still increased the infectivity of mutated SARS-CoV-2 pseudovirus in 293T-ACE2 cells when the canonical polybasic cleavage site (682–686) was deleted. However, K814A mutation eliminated the enhancing effect of furin on virus infection. Furin inhibitor prevented infection by 682–686-deleted SARS-CoV-2 in 293T-ACE2-furin cells, but not the K814A mutant. K814A mutation did not affect the activity of TMPRSS2 and cathepsin L but did impact the cleavage of S2 into S2′ and cell–cell fusion. Additionally, we showed that this functional furin site exists in RaTG13 from bat and PCoV-GD/GX from pangolin. Therefore, we discovered a new functional furin site that is pivotal in promoting SARS-CoV-2 infection.
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spelling pubmed-87412422022-01-08 A second functional furin site in the SARS-CoV-2 spike protein Zhang, Yue Zhang, Li Wu, Jiajing Yu, Yuanling Liu, Shuo Li, Tao Li, Qianqian Ding, Ruxia Wang, Haixin Nie, Jianhui Cui, Zhimin Wang, Yulin Huang, Weijin Wang, Youchun Emerg Microbes Infect Coronaviruses The ubiquitously-expressed proteolytic enzyme furin is closely related to the pathogenesis of SARS-CoV-2 and therefore represents a key target for antiviral therapy. Based on bioinformatic analysis and pseudovirus tests, we discovered a second functional furin site located in the spike protein. Furin still increased the infectivity of mutated SARS-CoV-2 pseudovirus in 293T-ACE2 cells when the canonical polybasic cleavage site (682–686) was deleted. However, K814A mutation eliminated the enhancing effect of furin on virus infection. Furin inhibitor prevented infection by 682–686-deleted SARS-CoV-2 in 293T-ACE2-furin cells, but not the K814A mutant. K814A mutation did not affect the activity of TMPRSS2 and cathepsin L but did impact the cleavage of S2 into S2′ and cell–cell fusion. Additionally, we showed that this functional furin site exists in RaTG13 from bat and PCoV-GD/GX from pangolin. Therefore, we discovered a new functional furin site that is pivotal in promoting SARS-CoV-2 infection. Taylor & Francis 2022-01-04 /pmc/articles/PMC8741242/ /pubmed/34856891 http://dx.doi.org/10.1080/22221751.2021.2014284 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Coronaviruses
Zhang, Yue
Zhang, Li
Wu, Jiajing
Yu, Yuanling
Liu, Shuo
Li, Tao
Li, Qianqian
Ding, Ruxia
Wang, Haixin
Nie, Jianhui
Cui, Zhimin
Wang, Yulin
Huang, Weijin
Wang, Youchun
A second functional furin site in the SARS-CoV-2 spike protein
title A second functional furin site in the SARS-CoV-2 spike protein
title_full A second functional furin site in the SARS-CoV-2 spike protein
title_fullStr A second functional furin site in the SARS-CoV-2 spike protein
title_full_unstemmed A second functional furin site in the SARS-CoV-2 spike protein
title_short A second functional furin site in the SARS-CoV-2 spike protein
title_sort second functional furin site in the sars-cov-2 spike protein
topic Coronaviruses
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741242/
https://www.ncbi.nlm.nih.gov/pubmed/34856891
http://dx.doi.org/10.1080/22221751.2021.2014284
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