Related Papers
Environmental Assisted Cracking resistance of High Grade Steel Pipeline in Real Operating Conditions
2016 •
Giuliano Malatesta
Physiological Genomics
Can cilia provide an entry gateway for SARS-CoV-2 to human ciliated cells?
2021 •
Kathleen Forero
A worldwide coronavirus pandemic is in full swing and, at the time of writing, there are only few treatments that have been successful in clinical trials, but no effective antiviral treatment has been approved. Because of its lethality, it is important to understand the current strain’s effects and mechanisms not only in the respiratory system but also in other affected organ systems as well. Past coronavirus outbreaks caused by SARS-CoV and MERS-CoV inflicted life-threatening acute kidney injuries (AKI) on their hosts leading to significant mortality rates, which went somewhat overlooked in the face of the severe respiratory effects. Recent evidence has emphasized renal involvement in SARS-CoV-2, stressing that kidneys are damaged in patients with COVID-19. The mechanism by which this virus inflicts AKI is still unclear, but evidence from other coronavirus strains may hold some clues. Two theories exist for the proposed mechanism of AKI: 1) the AKI is a secondary effect to reduced ...
Scientifica
A Review on Expression, Pathological Roles, and Inhibition of TMPRSS2, the Serine Protease Responsible for SARS-CoV-2 Spike Protein Activation
Sabarni Sarker
SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, uses the host cell membrane receptor angiotensin-converting enzyme 2 (ACE2) for anchoring its spike protein, and the subsequent membrane fusion process is facilitated by host membrane proteases. Recent studies have shown that transmembrane serine protease 2 (TMPRSS2), a protease known for similar role in previous coronavirus infections, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), is responsible for the proteolytic cleavage of the SARS-CoV-2 spike protein, enabling host cell fusion of the virus. TMPRSS2 is known to be expressed in the epithelial cells of different sites including gastrointestinal, respiratory, and genitourinary system. The infection site of the SARS-CoV-2 correlates with the coexpression sites of ACE2 and TMPRSS2. Besides, age-, sex-, and comorbidity-associated variation in infection rate correlates with the expression rate of TMPRSS2 in those groups. These f...
Nature Medicine
Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
2021 •
Yuk Ming Dennis Lo
Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells
2020 •
Linh Bui
ABSTRACTThe COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been asso...
SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery
2020 •
Carolina Garcia de Alba Rivas
Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. We developed primary human lung epithelial infection models to understand responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface cultures of proximal airway epithelium and 3D organoid cultures of alveolar epithelium were readily infected by SARS-CoV-2 leading to an epithelial cell-autonomous proinflammatory response. We validated the efficacy of selected candidate COVID-19 drugs confirming that Remdesivir strongly suppressed viral infection/replication. We provide a relevant platform for studying COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and future emergent respiratory pathogens.One Se...
SARS-CoV-2 Productively Infects Human Gut Enterocytes
Kèvin Knoops
COVID-19, caused by SARS-CoV-2, is an influenza-like disease with a respiratory route of transmission, yet clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids, enterocytes were readily infected by SARS-CoV and SARS-CoV-2 as demonstrated by confocal- and electron-microscopy. Consequently, significant titers of infectious viral particles were measured. mRNA expression analysis revealed strong induction of a generic viral response program. We conclude that intestinal epithelium supports SARS-CoV-2 replication.One Sentence SummarySARS-CoV-2 infection of enterocytes in human small intestinal organoids
Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue
2020 •
Quỳnh Cao
ABSTRACTIn December 2019, SARS-CoV-2 emerged causing the COVID-19 pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilizes ACE2 and TMPRSS2 host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147, and GRP78 may also function as receptors for SARS-CoV-2.To determine the expression and in situ localization of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analyzed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples.We demonstrate absent to low ACE2 promoter activity in a variety of lung epithelial cell samples and low ACE2 gene expression in both micr...
Annals of Cytology and Pathology
Pathologic basis of coronavirus disease 2019 (COVID-19) – An overview of cellular affinities, pathogenesis, clinical manifestations, autopsy findings and sequelae
2020 •
Magdalene Okoronkwo
Frontiers in Medicine
Air exposure and cell differentiation are essential for investigation of SARS-CoV-2 entry genes in human primary airway epithelial cells in vitro
2022 •
Brigitte Kasper
