Furin Protease: From SARS CoV-2 to Anthrax, Diabetes, and Hypertension

Fitzgerald, Kara

doi:10.7812/tpp/20.187

Cited by 19 publications

(8 citation statements)

References 16 publications

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“…For example, elevated furin expression negatively correlates with disease outcome in several cancers, increasing metastasis while reducing immune-cell infiltration [ 1 , 37 , 43 , 44 ]. Bioinformatic analyses identified FURIN polymorphisms as risk factors for diabetes, cardiovascular disease, obesity, and all-cause mortality [ 45 , 46 , 47 ]. Importantly, these furin-associated risk factors, together with furin’s key role in SARS-CoV-2 pathogenesis (as described below), may underpin the increased vulnerability of susceptible patients (including obese and diabetic patients) to negative outcomes from COVID-19 [ 48 , 49 ].…”

Section: Furin Essentialsmentioning

confidence: 99%

The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2

Thomas

Couture

Kwiatkowska

2022

IJMS

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The spurious acquisition and optimization of a furin cleavage site in the SARS-CoV-2 spike protein is associated with increased viral transmission and disease, and has generated intense interest in the development and application of therapeutic furin inhibitors to thwart the COVID-19 pandemic. This review summarizes the seminal studies that informed current efforts to inhibit furin. These include the convergent efforts of endocrinologists, virologists, and yeast geneticists that, together, culminated in the discovery of furin. We describe the pioneering biochemical studies which led to the first furin inhibitors that were able to block the disease pathways which are broadly critical for pathogen virulence, tumor invasiveness, and atherosclerosis. We then summarize how these studies subsequently informed current strategies leading to the development of small-molecule furin inhibitors as potential therapies to combat SARS-CoV-2 and other diseases that rely on furin for their pathogenicity and progression.

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Section: Furin Essentialsmentioning

confidence: 99%

The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2

Thomas

Couture

Kwiatkowska

2022

IJMS

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“…This cleavage allows the virus to shed the spike protein and enter the host cell. The use of the protease is thought to be a key component of the pathogenicity of many viruses, including SARS-CoV-2 infection ( Coutard et al, 2020 ; Fitzgerald, 2020 ). Of the known pathogenic beta coronaviruses, only the SARS-CoV2, MERS-CoV, and HCoV-OC43 viruses possess the FURIN cleavage complex motif.…”

Section: Sars-cov-2 Structural Proteins and Their Roles In Viral Entrymentioning

confidence: 99%

Impact of SARS-CoV-2 on Host Factors Involved in Mental Disorders

et al. 2022

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COVID-19, caused by SARS-CoV-2, is a systemic illness due to its multiorgan effects in patients. The disease has a detrimental impact on respiratory and cardiovascular systems. One early symptom of infection is anosmia or lack of smell; this implicates the involvement of the olfactory bulb in COVID-19 disease and provides a route into the central nervous system. However, little is known about how SARS-CoV-2 affects neurological or psychological symptoms. SARS-CoV-2 exploits host receptors that converge on pathways that impact psychological symptoms. This systemic review discusses the ways involved by coronavirus infection and their impact on mental health disorders. We begin by briefly introducing the history of coronaviruses, followed by an overview of the essential proteins to viral entry. Then, we discuss the downstream effects of viral entry on host proteins. Finally, we review the literature on host factors that are known to play critical roles in neuropsychiatric symptoms and mental diseases and discuss how COVID-19 could impact mental health globally. Our review details the host factors and pathways involved in the cellular mechanisms, such as systemic inflammation, that play a significant role in the development of neuropsychological symptoms stemming from COVID-19 infection.

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“…That is why furin can cleave the S protein in the Golgi complex and in the extracellular space [54]. The increased activity of furin in case of comorbidities such as hypertension, obesity and diabetes mellitus is probably one of the causes of the severe course of COVID-19 [55]. Furin convertase inhibitors-chloromethyl ketone and peptidyl chlromethyl ketones-are the promising agents for treating COVID-19 [56].…”

Section: Involvement Of Tmprss2 Adam17 and Furin In The Proteolysis O...mentioning

confidence: 99%

Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

Акбашева

Spirina

Dyakov

et al. 2022

Biochem. Moscow Suppl. Ser. B

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The SARS-CoV-2 pandemic had stimulated the emergence of numerous publications on the α 1 -proteinase inhibitor (α 1 -PI, α 1 -antitrypsin), especially when it was found that the regions of high mortality corresponded to the regions with deficient α 1 -PI alleles. By analogy with the data obtained in the last century, when the first cause of the genetic deficiency of α 1 -antitrypsin leading to elastase activation in pulmonary emphysema was proven, it can be supposed that proteolysis hyperactivation in COVID-19 may be associated with the impaired functions of α 1 -PI. The purpose of this review was to systematize the scientific data and critical directions for translational studies on the role of α 1 -PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a therapeutic target. This review describes the proteinase-dependent stages of viral infection: the reception and penetration of the virus into a cell and the imbalance of the plasma aldosterone–angiotensin–renin, kinin, and blood clotting systems. The role of ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases in the virus tropism, the activation of proteolytic cascades in blood, and the COVID-19-dependent complications is considered. The scientific reports on α 1 -PI involvement in the SARS-CoV-2-induced inflammation, the relationship with the severity of infection and comorbidities were analyzed. Particular attention is paid to the acquired α 1 -PI deficiency in assessing the state of patients with proteolysis overactivation and chronic non-inflammatory diseases, which are accompanied by the risk factors for comorbidity progression and the long-term consequences of COVID-19. Essential data on the search and application of protease inhibitor drugs in the therapy for bronchopulmonary and cardiovascular pathologies were analyzed. The evidence of antiviral, anti-inflammatory, anticoagulant, and anti-apoptotic effects of α 1 -PI, as well as the prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders, are presented.

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Furin Protease: From SARS CoV-2 to Anthrax, Diabetes, and Hypertension

Cited by 19 publications

References 16 publications

The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2

The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2

Impact of SARS-CoV-2 on Host Factors Involved in Mental Disorders

Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

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