The pivotal role of TMPRSS2 in coronavirus disease 2019 and prostate cancer

Mollica, Veronica; Rizzo, Alessandro; Massari, Francesco

doi:10.2217/fon-2020-0571

Cited by 141 publications

(141 citation statements)

References 29 publications

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“…This process is critical for virulence as it diminishes viral recognition by neutralizing antibodies and also helps in activating SARS-CoV-2 for virus cell fusion. That the activated androgen receptor regulates the transcriptional activity of the TMPRSS2 gene could partly explain the differential susceptibility of males for COVID-19 ( 42 , 43 ). TMPRSS2 works synergistically along with “a disintegrin and metalloproteinase domain-containing protein-17” (ADAM17) required for the shedding of ACE2 ( 44 ).…”

Section: Cell Invasion Gateways For Covid-19 and Similarities To Sarsmentioning

confidence: 99%

COVID-19 endocrinopathy with hindsight from SARS

Narasimhan

Anantharaj

Xue

et al. 2021

American Journal of Physiology-Endocrinology and Metabolism

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The current COVID-19 pandemic is probably the worst the world has ever faced since the start of the new millennium. While the respiratory system is the most prominent target of SARS-CoV-2 (the contagion of COVID-19), extra-pulmonary involvement are emerging as important contributors of its morbidity and lethality. This article summarizes the impact of SARS-CoV and SARS-CoV-2 on the endocrine system to facilitate our understanding of the nature of coronavirus-associated endocrinopathy. Although new data are rapidly accumulating on this novel infection, many of the endocrine manifestations of COVID-19 remain incompletely elucidated. We hereby summarize various endocrine dysfunctions including coronavirus-induced new onset diabetes mellitus, hypocortisolism, thyroid hormone and reproductive system aberrations so that clinicians armed with such insights can potentially benefit COVID-19 patients at the bedside.

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Section: Cell Invasion Gateways For Covid-19 and Similarities To Sarsmentioning

confidence: 99%

COVID-19 endocrinopathy with hindsight from SARS

Narasimhan

Anantharaj

Xue

et al. 2021

American Journal of Physiology-Endocrinology and Metabolism

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“…Testosterone and dihydrotestosterone regulate transcription of the TMPRSS2 gene through stimulation of the androgen receptor. 12 A disulphide bond links the catalytic domain and the membrane bound portion of the peptide; the protease domain is, however, released into the extracellular space. The N terminal is in the cytoplasm.…”

Section: Tmprss2 Structurementioning

confidence: 99%

“…Testosterone and dihydrotestosterone regulate transcription of the TMPRSS2 gene through stimulation of the androgen receptor. 12 …”

Section: Introductionmentioning

confidence: 99%

Gene of the month:TMPRSS2(transmembrane serine protease 2)

Thunders

Delahunt

2020

J Clin Pathol

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Transmembrane serine protease 2 is encoded by the TMPRSS2 gene. The gene is widely conserved and has two isoforms, both being autocatalytically activated from the inactive zymogen form. A fusion gene between the TMPRSS2 gene and ERG (erythroblast-specific-related gene), an oncogenic transcription factor, is the most common chromosomal aberration detected in prostate cancer, responsible for driving carcinogenesis. The other key role of TMPRSS2 is in priming the viral spike protein which facilitates viral entry essential for viral infectivity. The protease activates a diverse range of viruses. Both SARS-CoV and SARS-CoV-2 (COVID-19) use angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 to facilitate entry to cells, but with SARS-CoV-2 human-to-human transmission is much higher than SARS-CoV. As TMPRSS2 is expressed outside of the lung, and can therefore contribute to extrapulmonary spread of viruses, it warrants further exploration as a potential target for limiting viral spread and infectivity.

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“…The SARS-CoV virus admittance into the host cells is facilitated, either by endosomal cysteine proteases cathepsin L or by the cell membrane-associated serine protease TMPRSS2 by cleavage of the viral S protein [ 52 , 134 ]. The research findings in the literature suggest that, specifically, TMPRSS2 facilitates viral activation and is therefore considered as one of the essential host factors for SARS-CoV-2 pathogenicity [ 135 ].…”

Section: Potential Therapeutic Agents For Covid-19 Treatmentmentioning

confidence: 99%