Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects

Cheng, Ya Wen; Chao, Tai‐Ling; Li, Chiao Ling; Chiu, Mu Fan; Kao, Han Chieh; Wang, Sheng Han; Pang, Yi-Hsin; Lin, Chih Hui; Tsai, Ya Min; Lee, Wen Hau; Tao, Mi Hua; Ho, Tung Ching; Wu, Ping; Jang, Li Ting; Chen, Pei‐Jer; Chang, Sui‐Yuan; Yeh, Shiou Hwei

doi:10.1016/j.celrep.2020.108254

Cited by 226 publications

(254 citation statements)

References 52 publications

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“…Deletions of furin cleavage site in SARS-CoV-2 attenuates replication on respiratory cells ( Johnson et al, 2020 ) and pathogenesis in hamster ( Johnson et al, 2020 , Lau et al, 2020 ). Furin inhibitors suppress virus production and cytopathic effects in kidney cells ( Cheng et al, 2020 ). Natural polymorphisms losing furin recognition motif in SARS-CoV-2 spike S1/S2 are observed, but very rare ( Xing et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Furin cleavage sites naturally occur in coronaviruses

Zhao

2021

Stem Cell Research

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Section: Discussionmentioning

confidence: 99%

Furin cleavage sites naturally occur in coronaviruses

Zhao

2021

Stem Cell Research

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“… 66 Therefore, furin presents an additional pathway that could be pharmacologically targeted to curb the spread of SARS-CoV-2. 67 …”

Section: Sars-cov-2 Transmissionmentioning

confidence: 99%

COVID-19 Transmission, Current Treatment, and Future Therapeutic Strategies

et al. 2021

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At the stroke of the New Year 2020, COVID-19, a zoonotic disease that would turn into a global pandemic, was identified in the Chinese city of Wuhan. Although unique in its transmission and virulence, COVID-19 is similar to zoonotic diseases, including other SARS variants (e.g., SARS-CoV) and MERS, in exhibiting severe flu-like symptoms and acute respiratory distress. Even at the molecular level, many parallels have been identified between SARS and COVID-19 so much so that the COVID-19 virus has been named SARS-CoV-2. These similarities have provided several opportunities to treat COVID-19 patients using clinical approaches that were proven to be effective against SARS. Importantly, the identification of similarities in how SARS-CoV and SARS-CoV-2 access the host, replicate, and trigger life-threatening pathological conditions have revealed opportunities to repurpose drugs that were proven to be effective against SARS. In this article, we first provided an overview of COVID-19 etiology vis-a-vis other zoonotic diseases, particularly SARS and MERS. Then, we summarized the characteristics of droplets/aerosols emitted by COVID-19 patients and how they aid in the transmission of the virus among people. Moreover, we discussed the molecular mechanisms that enable SARS-CoV-2 to access the host and become more contagious than other betacoronaviruses such as SARS-CoV. Further, we outlined various approaches that are currently being employed to diagnose and symptomatically treat COVID-19 in the clinic. Finally, we reviewed various approaches and technologies employed to develop vaccines against COVID-19 and summarized the attempts to repurpose various classes of drugs and novel therapeutic approaches.

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“…These furin inhibitors might become promising antiviral agents for prevention and treatment of SARS-CoV-2 infections. 22 …”

Section: Basic Virologymentioning

confidence: 99%

Manipulation of ACE2 expression in COVID-19

et al. 2020

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SARS-CoV-2 is the virus responsible for the ongoing COVID-19 outbreak. The virus uses ACE2 receptor for viral entry. ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium. There is, however, significant controversy regarding the role of ACE2 expression in COVID-19 pathogenesis. Some have argued that decreasing ACE2 expression would result in decreased susceptibility to the virus by decreasing available binding sites for SARS-CoV-2 and restricting viral entry into the cells. Others have argued that, like the pathogenesis of other viral pneumonias, including those stemming from previous severe acute respiratory syndrome (SARS) viruses, once SARS-CoV-2 binds to ACE2, it downregulates ACE2 expression. Lack of the favourable effects of ACE2 might exaggerate lung injury by a variety of mechanisms. In order to help address this controversy, we conducted a literature search and review of relevant preclinical and clinical publications pertaining to SARS-CoV-2, COVID-19, ACE2, viral pneumonia, SARS, acute respiratory distress syndrome and lung injury. Our review suggests, although controversial, that patients at increased susceptibility to COVID-19 complications may have reduced baseline ACE2, and by modulating ACE2 expression one can possibly improve COVID-19 outcomes. Herein, we elucidate why and how this potential mechanism might work.

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Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects

Cited by 226 publications

References 52 publications

Furin cleavage sites naturally occur in coronaviruses

Furin cleavage sites naturally occur in coronaviruses

COVID-19 Transmission, Current Treatment, and Future Therapeutic Strategies

Manipulation of ACE2 expression in COVID-19

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