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 (ΔPRRA) 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 ΔPRRA 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 ΔPRRA mutant offered robust protection from SARS-CoV-2 rechallenge. Importantly, plaque reduction neutralization tests (PRNT 50 ) with COVID-19 patient sera and monoclonal antibodies against the receptor-binding domain found a shift, with the mutant virus resulting in consistently reduced PRNT 50 titers. Together, these results demonstrate a critical role for the furin cleavage site insertion in SARS-CoV-2 replication ...Continue Reading

Citations

Oct 28, 2020·Nature·Jessica A PlantePei-Yong Shi
Jan 14, 2021·The Biochemical Journal·George M Burslem
Jan 31, 2021·Nature Protocols·Xuping XiePei-Yong Shi
Nov 4, 2020·Biology Direct·Annalisa NoceNicola Di Daniele
Nov 15, 2020·Viruses·Lin Wang, Ye Xiang
Dec 17, 2020·Frontiers in Cellular and Infection Microbiology·Mei-Yue WangJi-Min Cao
Mar 16, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kenneth S PlanteRobert A Newman
Apr 1, 2021·Environmental Chemistry Letters·Rossana SegretoDaoyu Zhang
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Apr 13, 2021·The Journal of Clinical Investigation·Young Joo SunVinit B Mahajan

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Datasets Mentioned

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

Methods Mentioned

BETA
PCR
Assay

Related Concepts

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