Viral Cell Entry

All viruses require host cells for replication and for this they must enter the host cell. This process can be split into attachment of the virus to the host cell, mediated by a host cell surface receptor, entry into the cell by endocytosis and viral uncoating to release the viral genome into the cytoplasm.

Research Areas
Literature (2)

Mechanisms of SARS-CoV-2 Cell Entry

Entry of SARS-CoV-2, the coronavirus that causes COVID-19, into host cells begins with binding of the spike S protein on the virus binding to ACE2 expressed on the host cell surface. The S protein on the surface of SARS-CoV-2 is the largest protein within the virus and is heavily glycosylated. This protein forms extended trimeric structures that give this coronavirus its classical 'crown' shape. Disruption of S protein glycosylation has been shown to impair viral cell entry. A key difference between the S protein on SARS-CoV-2 and SARS-CoV, the cause of a previous outbreak of severe acute respiratory syndrome (SARS) in 2002-2004, is the presence of a cleavage site for furin at the S1/S2 ectodomain boundary on the SARS-CoV-2 S protein.

ACE2 is a transmembrane protease and its primary function is to cleave vasoactive peptides of the renin-angiotensin system. The S protein receptor binding domain (RBD) in the S1 ectodomain binds to the extracellular enzymatic domain of ACE2. ACE2 is also the cell surface receptor for SARS-CoV. However, other coronaviruses utilize different transmembrane proteases as their host cell receptor, for example MERS-CoV binds to dipeptidyl peptidase 4 (DPP-IV; CD26) and HCoV-229E binds to aminopeptidase N. Binding of the S protein to ACE2 is accompanied by 'priming' of the S protein by TMPRSS2, a host serine protease, which facilitate cell entry by cleaving the S protein at the boundry of S1/S2, or within the S2 domain. TMPRSS2 is coexpressed with ACE2 on human bronchial epithelial cells, a key site of SARS-CoV-2 infection in COVID-19.

Binding of the S protein to ACE2 results in endocytosis and translocation of the virus and ACE2 into endosomes located within the host cell. At this point, endosomal cathepsins B and L process the virus and the endosomes are acidified. The low pH of the endosomes and exposure to endosomal proteases are required to open the viral capsid. Subsequent mixing of the viral and endosomal membranes leads to release of the viral genome, in the form of positive-sense, single-stranded RNA, into the cytoplasm. At this point the virus co-opts the transcription and translation machinery of the host cell to replicate itself.

Literature for Viral Cell Entry

Tocris offers the following scientific literature for Viral Cell Entry to showcase our products. We invite you to request* or download your copy today!

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