Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview

Oubahmane, Mehdi; Hdoufane, Ismail; Bjij, Imane; Lahcen, Nouhaila Ait; Villemin, Didier; Daoud, Rachid; Allali, Achraf El; Cherqaoui, Driss

doi:10.2174/1568026622666220726122339

Cited by 10 publications

(6 citation statements)

References 142 publications

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“…anti-SARS-CoV-2 antibodies 35 ), as well as the relative quantity of the angiotensin converting enzyme-2 receptor, cellular proteases required for virus entry (e.g. TMPRSS-2 36 , 37 ), or other factors that impact the permissiveness of the cultured cells used. This can lead to discordance between the minimum virus concentration required for person-to-person transmission and that required for productive infection of cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of SARS-CoV-2 infection biomarkers in a household transmission study

Groh,

Vehreschild,

Diaz

et al. 2024

Sci Rep

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SARS-CoV-2 is the causative agent of COVID-19. Timely and accurate diagnostic testing is vital to contain the spread of infection, reduce delays in treatment and care, and inform patient management. Optimal specimen type (e.g. nasal swabs or saliva), timing of sampling, viral marker assayed (RNA or antigen), and correlation with viral infectivity and COVID-19 symptoms severity remain incompletely defined. We conducted a field study to evaluate SARS-CoV-2 viral marker kinetics starting from very early times after infection. We measured RNA and antigen levels in nasal swabs and saliva, virus outgrowth in cell culture from nasal swabs, and antibody levels in blood in a cohort of 30 households. Nine household contacts (HHC) became infected with SARS-CoV-2 during the study. Viral RNA was detected in saliva specimens approximately 1–2 days before nasal swabs in six HHC. Detection of RNA was more sensitive than of antigen, but antigen detection was better correlated with culture positivity, a proxy for contagiousness. Anti-nucleocapsid antibodies peaked one to three weeks post-infection. Viral RNA and antigen levels were higher in specimens yielding replication competent virus in cell culture. This study provides important data that can inform how to optimally interpret SARS-CoV-2 diagnostic test results.

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Section: Discussionmentioning

confidence: 99%

Kinetics of SARS-CoV-2 infection biomarkers in a household transmission study

Groh,

Vehreschild,

Diaz

et al. 2024

Sci Rep

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“…TMPRSS2 is a potential target for the treatment of COVID-19 due to its involvement in viral spike protein processing and localization in human epithelial tissues of the respiratory, genitourinary, and gastrointestinal tracts and its coexpression with the coronavirus receptor hACE2 in lung tissues. TMPRSS2 mediates viral entry through two distinct mechanisms: proteolytic cleavage of ACE2, which enhances viral uptake, and cleavage of the spike protein, which triggers host cell entry via membrane fusion 41 . Mice lacking TMPRSS2 exhibit no abnormalities in the absence of infection 42 , suggesting that blocking TMPRSS2 may not have significant undesired side effects.…”

Section: The Type II Transmembrane Serine Protease (Ttsp) Familymentioning

confidence: 99%

TMPRSS4, a type II transmembrane serine protease, as a potential therapeutic target in cancer

Kim

2023

Exp Mol Med

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Proteases are involved in almost all biological processes, implying their importance for both health and pathological conditions. Dysregulation of proteases is a key event in cancer. Initially, research identified their role in invasion and metastasis, but more recent studies have shown that proteases are involved in all stages of cancer development and progression, both directly through proteolytic activity and indirectly via regulation of cellular signaling and functions. Over the past two decades, a novel subfamily of serine proteases called type II transmembrane serine proteases (TTSPs) has been identified. Many TTSPs are overexpressed by a variety of tumors and are potential novel markers of tumor development and progression; these TTSPs are possible molecular targets for anticancer therapeutics. The transmembrane protease serine 4 (TMPRSS4), a member of the TTSP family, is upregulated in pancreatic, colorectal, gastric, lung, thyroid, prostate, and several other cancers; indeed, elevated expression of TMPRSS4 often correlates with poor prognosis. Based on its broad expression profile in cancer, TMPRSS4 has been the focus of attention in anticancer research. This review summarizes up-to-date information regarding the expression, regulation, and clinical relevance of TMPRSS4, as well as its role in pathological contexts, particularly in cancer. It also provides a general overview of epithelial-mesenchymal transition and TTSPs.

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“…Three years after the emergence of the COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the entire world is still suffering from the major health and socioeconomic consequences of the disease [1]. Accordingly, significant research efforts have been made to develop vaccines and drugs to effectively stop COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Design of Potent Inhibitors Targeting the Main Protease of SARS-CoV-2 Using QSAR Modeling, Molecular Docking, and Molecular Dynamics Simulations

Oubahmane¹,

Hdoufane²,

Delaite

et al. 2023

Pharmaceuticals

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a serious global public health threat. The evolving strains of SARS-CoV-2 have reduced the effectiveness of vaccines. Therefore, antiviral drugs against SARS-CoV-2 are urgently needed. The main protease (Mpro) of SARS-CoV-2 is an extremely potent target due to its pivotal role in virus replication and low susceptibility to mutation. In the present study, a quantitative structure–activity relationship (QSAR) study was performed to design new molecules that might have higher inhibitory activity against SARS-CoV-2 Mpro. In this context, a set of 55 dihydrophenanthrene derivatives was used to build two 2D-QSAR models using the Monte Carlo optimization method and the Genetic Algorithm Multi-Linear Regression (GA-MLR) method. From the CORAL QSAR model outputs, the promoters responsible for the increase/decrease in inhibitory activity were extracted and interpreted. The promoters responsible for an increase in activity were added to the lead compound to design new molecules. The GA-MLR QSAR model was used to ensure the inhibitory activity of the designed molecules. For further validation, the designed molecules were subjected to molecular docking analysis and molecular dynamics simulations along with an absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. The results of this study suggest that the newly designed molecules have the potential to be developed as effective drugs against SARS-CoV-2.

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Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview

Cited by 10 publications

References 142 publications

Kinetics of SARS-CoV-2 infection biomarkers in a household transmission study

Kinetics of SARS-CoV-2 infection biomarkers in a household transmission study

TMPRSS4, a type II transmembrane serine protease, as a potential therapeutic target in cancer

Design of Potent Inhibitors Targeting the Main Protease of SARS-CoV-2 Using QSAR Modeling, Molecular Docking, and Molecular Dynamics Simulations

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