FURIN cleavage site (PRRAR): don't forget possible & likely KEY role in this COVID pathogen as it is missing in other group 2B corona viruses; a critical role in infection as seen in mutant

by Paul Alexander

COVID virus; mutant virus (furin removed) has reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis.

Bottom line is research showed that if you removed the furin cleavage site, it mitigates infection (replication) and weakens the COVID virus (note distinction between infection and COVID disease, as one can be infected with a pathogen but not have the disease with symptoms). Clear evidence that this spcialized site (delibrately inserted) enhances infection/replication and pathogenicity.

AwakeNotWoke reminded me and I ask you to support this substack, good writing, very good work!!

 

SOURCE:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175039/

‘SARS-CoV-2, a novel coronavirus (CoV) producing worldwide pandemic1, has a furin cleavage site (PRRAR) in its spike protein that is absent in other group 2B CoVs 2.

To explore whether the furin cleavage site contributes to infection and pathogenesis, we generated a mutant SARS-CoV-2 deleting the furin cleavage site (ΔPRRA).

SARS-CoV-2 ΔPRRA replicates with faster kinetics, has improved fitness in Vero E6 cells, and has reduced spike protein processing as compared to parental SARS-CoV-2.

However, the ΔPRRA mutant has reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis.

Despite reduced disease, the ΔPRRA mutant conferred protection against rechallenge with the parental SARS-CoV-2.

Importantly, COVID-19 patient sera and receptor-binding domain (RBD) monoclonal antibodies had lower neutralization values against the ΔPRRA mutant versus parental SARS-CoV-2 likely due to increased particle/PFU ratio.

Together, these results demonstrate a critical role for the furin cleavage site in SARS-CoV-2 infection and highlight the importance of this site in evaluating antibody neutralization activity.’