Low expression of TMPRSS2–a SARS-CoV-2 internalization protease–associates with basal subtype of head and neck squamous cell carcinoma

Tiwari, Jayesh; Tripathi, Nancy; Srivastava, Ravi Shanker; Kumar, Sujeet; Singh, Sanjay; Jain, Shreyans K.; Khattri, Arun

doi:10.1016/j.tranon.2022.101458

Cited by 5 publications

(4 citation statements)

References 14 publications

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“…The negative association between SARS-CoV-2 infection and head and neck cancer patients might be because the head and neck cancer expressed a low SARS-CoV-2 internalization protease TMPRSS2. 42,43…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we inferred that the high expression level of ACE2 in HER2‐positive BC was linked with the susceptibility to SARS‐CoV‐2 infection and cancer risk. The negative association between SARS‐CoV‐2 infection and head and neck cancer patients might be because the head and neck cancer expressed a low SARS‐CoV‐2 internalization protease TMPRSS2 42,43 . Therefore, COVID‐19 patients with a high level of TMPRSS2 may be less likely to increase the risk of head and neck cancer.…”

Section: Discussionmentioning

confidence: 99%

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Causal effects of COVID‐19 on cancer risk: A Mendelian randomization study

Bai

Hao

et al. 2023

Journal of Medical Virology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Causal effects of COVID‐19 on cancer risk: A Mendelian randomization study

Bai

Hao

et al. 2023

Journal of Medical Virology

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“…23.537985 doi: bioRxiv preprint overexpressed in different cancer types, notably prostate, invasive breast, head and neck cancers, and lung carcinoma, making it an attractive biomarker for the early diagnosis. [5][6][7] TMPRSS2 is related to carcinogenesis, cancer metastatic progression, 8,9 and its role on the chronic pain experienced by patients has also been stressed out. 10 Indeed, its localization at the surface of cancer cells allows the protein to mediate, via its proteolytic activity, different signaling cascades and transduction between the cells and the extracellular medium, including pain signals.…”

Section: Toc Graphicsmentioning

confidence: 99%

Mechanism of the Covalent Inhibition of Human Transmembrane Protease Serine 2 as an Original Antiviral Strategy

Spinello¹,

D'Anna²,

Bignon

et al. 2023

Preprint

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The Transmembrane Protease Serine 2 (TMPRSS2) is a human enzyme which is involved in the maturation and post-translation of different proteins. In addition of being overexpressed in cancer cells, TMPRSS2 plays a further fundamental role in favoring viral infections by allowing the fusion of the virus envelope and the cellular membrane, notably in SARS-CoV-2. In this contribution we resort to multiscale molecular modeling to unravel the structural and dynamical features of TMPRSS2 and its interaction with a model lipid bilayer. Furthermore, we shed light into the mechanism of action of a potential inhibitor (Nafamostat), determining the free-energy profile associated with the inhibition reaction, and showing the facile poisoning of the enzyme. Our study, while providing the first atomistically resolved mechanism of TMPRSS2 inhibition, is also fundamental in furnishing a solid framework for further rational design targeting transmembrane proteases in a host-directed antiviral strategy.

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“…Interestingly, TMPRSS2 and the related proteins are also involved in key epithelial homeostatic regulation . Furthermore, TMPRSS2 is highly overexpressed in different cancer types, notably prostate, invasive breast, head and neck cancers, and lung carcinoma, making it an attractive biomarker for early diagnosis. − TMPRSS2 is related to carcinogenesis and cancer metastatic progression, , and its role in the chronic pain experienced by patients has also been stressed out . Indeed, its localization at the surface of cancer cells allows the protein to mediate, via its proteolytic activity, different signaling cascades and transduction between the cells and the extracellular medium, including pain signals.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the Covalent Inhibition of Human Transmembrane Protease Serine 2 as an Original Antiviral Strategy

et al. 2023

View full text Add to dashboard Cite

The Transmembrane Protease Serine 2 (TMPRSS2) is a human enzyme which is involved in the maturation and post-translation of different proteins. In addition to being overexpressed in cancer cells, TMPRSS2 plays a further fundamental role in favoring viral infections by allowing the fusion of the virus envelope with the cellular membrane, notably in SARS-CoV-2. In this contribution, we resort to multiscale molecular modeling to unravel the structural and dynamical features of TMPRSS2 and its interaction with a model lipid bilayer. Furthermore, we shed light on the mechanism of action of a potential inhibitor (nafamostat), determining the free-energy profile associated with the inhibition reaction and showing the facile poisoning of the enzyme. Our study, while providing the first atomistically resolved mechanism of TMPRSS2 inhibition, is also fundamental in furnishing a solid framework for further rational design targeting transmembrane proteases in a host-directed antiviral strategy.

show abstract

Low expression of TMPRSS2–a SARS-CoV-2 internalization protease–associates with basal subtype of head and neck squamous cell carcinoma

Cited by 5 publications

References 14 publications

Causal effects of COVID‐19 on cancer risk: A Mendelian randomization study

Causal effects of COVID‐19 on cancer risk: A Mendelian randomization study

Mechanism of the Covalent Inhibition of Human Transmembrane Protease Serine 2 as an Original Antiviral Strategy

Mechanism of the Covalent Inhibition of Human Transmembrane Protease Serine 2 as an Original Antiviral Strategy

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