Cell entry by SARS-CoV-2

Abstract

The severe acute respiratory syndrome virus 2 (SARS-CoV-2) invades host cells by interacting with receptors/co-receptors, as well as other co-factors, via its spike (S) protein that further mediates the fusion between viral and cellular membranes. The host membrane protein angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV-2 and a critical determinant for its cross-species transmission. Additionally, some auxiliary receptors and co-factors are also involved which would expand the host/tissue tropism of SARS-CoV-2. After receptor engagement, certain proteases are required to cleave the S protein to trigger its fusogenic activity. In this review, we discuss the recent advancement in understanding the molecular events during SARS-CoV-2 entry which would contribute to developing vaccines and therapeutics.

Inducible CRISPR activation screen for interferon-stimulated genes identifies OAS1 as a SARS-CoV-2 restriction factor

“…Coronaviruses can enter cells via two different routes: from the cell membrane or from the endosomal compartment. The route of entry is determined in part by the presence of cellular proteases required for spike protein processing 79 . SARS-CoV-2 entry from the cell surface requires TMPRSS2 , while endosomal entry is mediated by cathepsins that process the spike protein 79 .…”

Cell Fusion as a Link between the SARS-CoV-2 Spike Protein, COVID-19 Complications, and Vaccine Side Effects

“…1 What are the properties of, say, a syncytium that is made up of a pneumocyte with an epithelial progenitor? What happens if a leukocyte or another cell that carries one of spike receptors 48 joins in? Moreover, SARS-CoV-2 may not be the only virus that makes syncytia in COVID-19.…”

“…To improve the immune response, the developers 76,77,79 have stabilized spike structure by two mutations that suppress a conformational change triggered by binding to ACE2. 94,95 Because this change is involved in spike activation, 48 suppressing it has also inhibited cell fusion in a tissue culture assay by several fold. 77 Two additional mutations introduced in the Janssen vaccine decreased this incidence in the same assay further 77 by altering the site recognized by furin, a protease that contributes to spike activation by cleaving it into two subunits.…”

“…Some complications caused by cell fusion may be specific to a particular vaccine or to COVID-19 because the tropisms of adenoviral vectors, mRNA-carrying lipid particles, and SARS-CoV-2 overlap but are not identical. 48,114,115 A contributing factor could be a predisposition of some individuals to cell fusion by viral fusogens, which is difficult to evaluate at this time because cell fusion regulation in general and the regulation of cell fusion induced by viruses in particular is still largely a terra incognita.…”

Nanovaccines against Animal Pathogens: The Latest Findings

“…This is exemplified by zoonotic coronaviruses and the latest SARS-CoV-2 virus showing receptor orthologs widely distributed in various domestic and wild mammals in which COVID-19 appears. Furthermore, it is clear that viral persistence may be facilitated by a number of macro-ecological characteristics, in turn contributing to variation and a proclivity for specific hosts [10][11][12][13][14][15]. The potential transmission of pathogens currently affecting humans to animal populations has highlighted the need to adopt a One Health approach regarding global health interventions.…”