TY - JOUR T1 - A second functional furin site in the SARS-CoV-2 spike protein. AU - Zhang,Yue, AU - Zhang,Li, AU - Wu,Jiajing, AU - Yu,Yuanling, AU - Liu,Shuo, AU - Li,Tao, AU - Li,Qianqian, AU - Ding,Ruxia, AU - Wang,Haixin, AU - Nie,Jianhui, AU - Cui,Zhimin, AU - Wang,Yulin, AU - Huang,Weijin, AU - Wang,Youchun, PY - 2021/12/4/pubmed PY - 2022/1/18/medline PY - 2021/12/3/entrez KW - S2’ cleavage KW - SARS-CoV-2 KW - cell–cell fusion KW - furin KW - infectivity KW - pseudovirus SP - 182 EP - 194 JF - Emerging microbes & infections JO - Emerg Microbes Infect VL - 11 IS - 1 N2 - 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. SN - 2222-1751 UR - https://www.unboundmedicine.com/medline/citation/34856891/A_second_functional_furin_site_in_the_SARS_CoV_2_spike_protein_ DB - PRIME DP - Unbound Medicine ER -