Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), like other coronaviruses, relies on a flexible array of entry mechanisms, driven by the spike (S) protein. Entry is dependent on proteolytic priming, activation, and receptor binding; all of which can be variable, dependent on context. Here we review the implications of the complexity of SARS-CoV-2 entry pathways on entry assays that then drive our understanding of humoral immunity, therapeutic efficacy, and tissue restriction. We focus especially on the proteolytic activation of SARS-CoV-2 spike and how this constellation of proteases lends deeper insight to our understanding of arising variants and their putative role transmission or variable pathogenicity in vivo. In this review, we argue for better universal standards to assay virus entry as well as suggest best practices for reporting viral passage number, the cell line used, and proteases present, among other important considerations.
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http://dx.doi.org/10.1016/j.coviro.2021.07.004 | DOI Listing |
Int J Mol Sci
December 2024
Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that emerged in late 2019 and rapidly spread worldwide, causing the COVID-19 pandemic. The spike glycoprotein (S protein) plays a crucial role in viral target recognition and entry by interacting with angiotensin, converting enzyme 2 (ACE2), the functional receptor for the virus, via its receptor binding domain (RBD). The RBD availability for this interaction can be influenced by external factors, such as fatty acids.
View Article and Find Full Text PDFSci Adv
January 2025
Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used an engineered angiotensin-converting enzyme 2 to capture intact virus from plasma and other complex biofluids.
View Article and Find Full Text PDFJ Virol
January 2025
Infection Biology Unit, German Primate Centre - Leibniz Institute for Primate Research, Göttingen, Germany.
The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether the cellular proteins ASGR1, DC-SIGN, and TMEM106B, which interact with the viral S protein, can contribute to these processes. Employing S protein-pseudotyped particles, we found that expression of ASGR1 or DC-SIGN jointly with TMEM106B allowed for robust entry of mutant E484D into otherwise non-susceptible cells, while this effect was not observed upon separate expression of the single proteins and upon infection with SARS-CoV-2 wild type (WT).
View Article and Find Full Text PDFTissue Cell
December 2024
Laboratory of Teaching and Research in Histology and Comparative Embryology (LEPHEC), Biomedical Institute, Fluminense Federal University, Niterói, RJ CEP 24210-130, Brazil. Electronic address:
SARS-Cov-2 is a corona virus that causes COVID-19 disease, a viral infection responsible for the pandemic decreed by the World Health Organization in March 2020. Angiotensin-converting enzyme 2 (ACE-2) functions as the main receptor for SARS-Cov-2. The study aimed to detect the expression of ACE-2 in the gastrointestinal tract, kidney, and lung in the rhesus monkeys and squirrel monkeys.
View Article and Find Full Text PDFSignal Transduct Target Ther
January 2025
The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
The mucosal immune system, as the most extensive peripheral immune network, serves as the frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion and establishing immune tolerance. A comprehensive understanding of mucosal immunity is essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing the overall impact on the body.
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