General Information:

Id: 11,827 (click here to show other Interactions for entry)
Diseases: COVID-19
Homo sapiens
article
Reference: Hoffmann M et al.(2020) SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor Cell 181: 271-280.e8 [PMID: 32142651]

Interaction Information:

Comment The spike (S) protein of coronaviruses facilitates viral entry into target cells. Entry depends on binding of the surface unit, S1, of the S protein to a cellular receptor, which facilitates viral attachment to the surface of target cells. In addition, entry requires S protein priming by cellular proteases, which entails S protein cleavage at the S1/S2 and the S2’ site and allows fusion of viral and cellular membranes, a process driven by the S2 subunit. The goal of this study was to obtain insights into how SARS-2-S facilitates viral entry into target cells and how this process can be blocked. Directed expression of human and bat (Rhinolophus alcyone) ACE2 but not human DPP4, the entry receptor used by MERS-CoV, or human APN, the entry receptor used by HCoV-229E, allowed SARS-2-S- and SARS-S-driven entry into otherwise non-susceptible BHK-21 cells. Moreover, anti-serum raised against human ACE2 blocked SARS-S- andSARS-2-S- but not VSV-G- or MERS-S-driven entry. Finally, authentic SARS-CoV-2 infected BHK-21 cells transfected to express ACE2 cells but not parental BHK-21 cells with high efficiency, indicating that SARS-2-S, like SARS-S, uses ACE2 for cellular entry.
Formal Description
Interaction-ID: 116824

environment

SARS-CoV-2 S protein

interacts (colocalizes) with

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment SARS-CoV can use the endosomal cysteine proteases cathepsin B and L (CatB/L) and the serineprotease TMPRSS2 for S protein priming in cell lines, and inhibition of both proteases is required for robust blockade of viral entry. However, only TMPRSS2 activity is essential for viral spread and pathogenesis in the infected host whereas CatB/L activity is dispensable. This study shows that SARS-CoV-2 can use TMPRSS2 for S protein priming and camostat mesylate, an inhibitor of TMPRSS2, blocks SARS-CoV-2 infection of lung cells.
Formal Description
Interaction-ID: 116872

gene/protein

TMPRSS2

increases_activity of

environment

SARS-CoV-2 S protein

Comment SARS-CoV can use the endosomal cysteine proteases cathepsin B and L (CatB/L) and the serineprotease TMPRSS2 for S protein priming in cell lines, and inhibition of both proteases is required for robust blockade of viral entry. However, only TMPRSS2 activity is essential for viral spread and pathogenesis in the infected host whereas CatB/L activity is dispensable. This study shows that SARS-CoV-2 can use TMPRSS2 for S protein priming and camostat mesylate, an inhibitor of TMPRSS2, blocks SARS-CoV-2 infection of lung cells.
Formal Description
Interaction-ID: 116877

drug/chemical compound

Camostat mesilate

decreases_activity of

gene/protein

TMPRSS2

in lung cells