Cargando…

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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario: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.