Furin: A Potential Therapeutic Target for COVID-19

Wu, Canrong; Zheng, Mengzhu; Yang, Yueying; Gu, Xiaoxia; Yang, Kaiyin; Li, Mingxue; Liu, Yang; Zhang, Qingzhe; Zhang, Peng; Wang, Yali; Wang, Qiqi; Xu, Yu; Zhou, Yirong; Zhang, Yonghui; Chen, Lixia; Li, Hua

doi:10.1016/j.isci.2020.101642

Cited by 159 publications

(159 citation statements)

References 30 publications

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“…Studies had reported both the respiratory and gastrointestinal tract manifestations of COVID-19 (4,32). As mentioned before, the ACE2 receptor in the host cell membrane and Furin cleavage site of SARS-CoV-2 are the key factors that allowed the virus to invade the host cells (22,23). In this study, we found the expression of ACE2 and Furin in oral epithelial cells in both mRNA and protein levels.…”

Section: Discussionmentioning

confidence: 95%

“…Genomic characterization of SARS-CoV-2 has revealed that the Furin enzyme could activate the specific site of its spike protein (21). Meanwhile, Li et al (22) showed that a putative Furin cleavage site in the spike protein of SARS-CoV-2 facilitates the virus-cell fusion. The Furin cleavage site is absent in SARS-CoV.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of the Furin cleavage site in SARS-CoV-2 showed distinct clinical symptoms (23,24). Furthermore, online single-cell sequence datasets analysis unveiled that Furin was expressed in coronavirus's potential target organs, such as lung, heart, nose, rectum, colon, intestine, and ileum (22). Hence, the expression and distribution of ACE2 and Furin in the epithelium of the oral cavity could be critical for the coronavirus invasion to the host cells.…”

Section: Introductionmentioning

confidence: 99%

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ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal–Oral Routes

et al. 2020

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Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear.Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level.Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results.Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal–oral routes.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal–Oral Routes

et al. 2020

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“…In addition to ACE2, COVID-19 infection is also dependent on other cellular proteins, such as Furin. The spike protein of SARS-CoV-2 contains a furin cleavage site, the unique RRAR motif; which was not found in any other subtype B betacoronavirus ( 30 ). Male and elder people, as well as obese and diabetic patients, have increased levels of furin in their blood ( 6 ), making this enzyme a potential therapeutic target of COVID-19 in those subjects ( 6 , 30 ).…”

Section: The Hypertension Medicines Aceis and Arbsmentioning

confidence: 95%

“…The spike protein of SARS-CoV-2 contains a furin cleavage site, the unique RRAR motif; which was not found in any other subtype B betacoronavirus ( 30 ). Male and elder people, as well as obese and diabetic patients, have increased levels of furin in their blood ( 6 ), making this enzyme a potential therapeutic target of COVID-19 in those subjects ( 6 , 30 ). It is worth to test whether furin inhibitors, including the flavone Luteolin, isolated from Chinese herbal medicine ( 31 ), can prevent the COVID-19 infection and virus replication.…”

Section: The Hypertension Medicines Aceis and Arbsmentioning

confidence: 95%

Friend or foe? ACE2 inhibitors and GLP-1R agonists in COVID-19 treatment

et al. 2021

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Might SARS‐CoV‐2 Have Arisen via Serial Passage through an Animal Host or Cell Culture?

Sirotkin¹,

Sirotkin²

2020

BioEssays

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Despite claims from prominent scientists that SARS-CoV-2 indubitably emerged naturally, the etiology of this novel coronavirus remains a pressing and open question: Without knowing the true nature of a disease, it is impossible for clinicians to appropriately shape their care, for policy-makers to correctly gauge the nature and extent of the threat, and for the public to appropriately modify their behavior. Unless the intermediate host necessary for completing a natural zoonotic jump is identified, the dual-use gain-of-function research practice of viral serial passage should be considered a viable route by which the novel coronavirus arose. The practice of serial passage mimics a natural zoonotic jump, and offers explanations for SARS-CoV-2's distinctive spike-protein region and its unexpectedly high affinity for angiotensin converting enzyme (ACE2), as well as the notable polybasic furin cleavage site within it. Additional molecular clues raise further questions, all of which warrant full investigation into the novel coronavirus's origins and a re-examination of the risks and rewards of dual-use gain-of-function research.

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Furin: A Potential Therapeutic Target for COVID-19

Cited by 159 publications

References 30 publications

ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal–Oral Routes

ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal–Oral Routes

Friend or foe? ACE2 inhibitors and GLP-1R agonists in COVID-19 treatment

Might SARS‐CoV‐2 Have Arisen via Serial Passage through an Animal Host or Cell Culture?

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