Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges

Mahmoud, Ismail Sami; Jarrar, Yazun

doi:10.1007/s11033-021-06390-1

Cited by 12 publications

(10 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TMPRSS2 also aided modeling of URI frequency. Prior studies have found that TMPRSS2 promotes viral propagation by activating the spike protein and enhancing viral entry into host cells in severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV) [ 24 ]. It is possible that the infant upper respiratory tract responds to recurrent viral URI infections by down-regulating TMPRSS2 expression in an effort to reduce URI frequency.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omic Factors Associated with Frequency of Upper Respiratory Infections in Developing Infants

Beheshti

Halstead

Cusack

et al. 2023

IJMS

View full text Add to dashboard Cite

Susceptibility to upper respiratory infections (URIs) may be influenced by host, microbial, and environmental factors. We hypothesized that multi-omic analyses of molecular factors in infant saliva would identify complex host-environment interactions associated with URI frequency. A cohort study involving 146 infants was used to assess URI frequency in the first year of life. Saliva was collected at 6 months for high-throughput multi-omic measurement of cytokines, microRNAs, transcripts, and microbial RNA. Regression analysis identified environmental (daycare attendance, atmospheric pollution, breastfeeding duration), microbial (Verrucomicrobia, Streptococcus phage), and host factors (miR-22-5p) associated with URI frequency (p < 0.05). These results provide pathophysiologic clues about molecular factors that influence URI susceptibility. Validation of these findings in a larger cohort could one day yield novel approaches to detecting and managing URI susceptibility in infants.

show abstract

Section: Discussionmentioning

confidence: 99%

Multi-Omic Factors Associated with Frequency of Upper Respiratory Infections in Developing Infants

Beheshti

Halstead

Cusack

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The pathophysiology of SARS-CoV-2 infection in gastrointestinal tissues may depend on many factors 59 – 61 . Not only normal GI tissues but also GI tumors may easily be infected by pathogens due to their distinct mucosal membrane protein expression profiles.…”

Section: Discussionmentioning

confidence: 99%

Increased TRIM31 gene expression is positively correlated with SARS-CoV-2 associated genes TMPRSS2 and TMPRSS4 in gastrointestinal cancers

Temena

Acar

2022

Sci Rep

View full text Add to dashboard Cite

Besides typical respiratory symptoms, COVID-19 patients also have gastrointestinal symptoms. Studies focusing on the gastrointestinal tumors derived from gastrointestinal tissues have raised a question whether these tumors might express higher levels of SARS-CoV-2 associated genes and therefore patients diagnosed with GI cancers may be more susceptible to the infection. In this study, we have analyzed the expression of SARS-CoV-2 associated genes and their co-expressions in gastrointestinal solid tumors, cancer cell lines and patient-derived organoids relative to their normal counterparts. Moreover, we have found increased co-expression of TMPRSS2-TMPRSS4 in gastrointestinal cancers suggesting that SARS-CoV-2 viral infection known to be mediated by this protease pair might facilitate the effects of viral infection in GI cancer patients. Further, our findings also demonstrate that TRIM31 expression is upregulated in gastrointestinal tumors, while the inhibition of TRIM31 significantly altered viral replication and viral processes associated with cellular pathways in gastrointestinal cancer samples. Taken together, these findings indicate that in addition to the co-expression of TMPRSS2-TMPRSS4 protease pair in GI cancers, TRIM31 expression is positively correlated with this pair and TRIM31 may play a role in providing an increased susceptibility in GI cancer patients to be infected with SARS-CoV-2 virus.

show abstract

“…Targeting SARS-CoV-2 entry factors, including TMPRSS2, may be a therapeutic strategy against COVID-19 [ 32 , 33 , 34 ]. Molecular docking analysis has predicted that small molecules have a functional inhibitory effect on TMPRSS2 [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2

Tan

Liu

et al. 2022

Molecules

View full text Add to dashboard Cite

As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was significantly associated with a short overall survival in breast invasive carcinoma (BRCA), sarcoma (SARC), and uveal melanoma (UVM), while a low expression of TMPRSS2 was significantly associated with a short overall survival in lung adenocarcinoma (LUAD), demonstrating TMPRSS2 roles in cancer patient susceptibility and severity. Additionally, TMPRSS2 expression in COVID-19-infected lung tissues was significantly reduced compared to healthy lung tissues, indicating that a low TMPRSS2 expression may result in COVID-19 severity and death. Importantly, TMPRSS2 mutation frequency was significantly higher in prostate adenocarcinoma (PRAD), and the mutant TMPRSS2 pan-cancer group was significantly associated with long overall, progression-free, disease-specific, and disease-free survival rates compared to the wild-type (WT) TMPRSS2 pan-cancer group, demonstrating loss of functional roles due to mutation. Cancer cell lines were treated with small molecules, including cordycepin (CD), adenosine (AD), thymoquinone (TQ), and TQFL12, to mediate TMPRSS2 expression. Notably, CD, AD, TQ, and TQFL12 inhibited TMPRSS2 expression in cancer cell lines, including the PC3 prostate cancer cell line, implying a therapeutic role for preventing COVID-19 in cancer patients. Together, these findings are the first to demonstrate that small molecules, such as CD, AD, TQ, and TQFL12, inhibit TMPRSS2 expression, providing novel therapeutic strategies for preventing COVID-19 and cancers.

show abstract

Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges

Cited by 12 publications

References 70 publications

Multi-Omic Factors Associated with Frequency of Upper Respiratory Infections in Developing Infants

Multi-Omic Factors Associated with Frequency of Upper Respiratory Infections in Developing Infants

Increased TRIM31 gene expression is positively correlated with SARS-CoV-2 associated genes TMPRSS2 and TMPRSS4 in gastrointestinal cancers

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2

Contact Info

Product

Resources

About