Furin Cleavage Site Is Key to SARS-CoV-2 Pathogenesis

BioRxiv : the Preprint Server for Biology
Bryan A JohnsonVineet D Menachery

Abstract

SARS-CoV-2 has resulted in a global pandemic and shutdown economies around the world. Sequence analysis indicates that the novel coronavirus (CoV) has an insertion of a furin cleavage site (PRRAR) in its spike protein. Absent in other group 2B CoVs, the insertion may be a key factor in the replication and virulence of SARS-CoV-2. To explore this question, we generated a SARS-CoV-2 mutant lacking the furin cleavage site ({Delta}PRRA) in the spike protein. This mutant virus replicated with faster kinetics and improved fitness in Vero E6 cells The mutant virus also had reduced spike protein processing as compared to wild-type SARS-CoV-2. In contrast, the {Delta}PRRA had reduced replication in Calu3 cells, a human respiratory cell line, and had attenuated disease in a hamster pathogenesis model. Despite the reduced disease, the {Delta}PRRA mutant offered robust protection from SARS-CoV-2 rechallenge. Importantly, plaque reduction neutralization tests (PRNT50) with COVID-19 patient sera and monoclonal antibodies against the receptor-binding domain found a shift, with the mutant virus resulting in consistently reduced PRNT50 titers. Together, these results demonstrate a critical role for the furin cleavage site insertion in SARS-CoV-...Continue Reading

Datasets Mentioned

BETA
QHU79204
QND76034.1
AGZ48828.1
AGZ48806
ALK02457
AYV99817.1

Methods Mentioned

BETA
PCR
Assay

Software Mentioned

umi
MiSeq Reporter
Prism
Model
bowtie
SWISS
bedtools
GraphPad
ImageLab
Geneious

Related Concepts

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