ABSTRACT 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.
【저자키워드】 SARS-CoV-2, furin, Infectivity, pseudovirus, cell–cell fusion, S2’ cleavage, TMPRSS2, 【초록키워드】 antiviral therapy, Mutation, SARS-COV-2 infection, Infection, cells, RaTG13, cleavage, SARS-CoV-2 pseudovirus, mutant, virus infection, inhibitor, cathepsin L, enzyme, furin site, cleavage site, bioinformatic analysis, pathogenesis of SARS-CoV-2, functional, the spike protein, not affect, mutated, prevented, deleted, canonical, 293T-ACE2 cell, eliminated, polybasic, proteolytic, 【제목키워드】 Spike protein, furin site, functional, the SARS-CoV-2,