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Oxford University Press - PMC COVID-19 Collection logoLink to Oxford University Press - PMC COVID-19 Collection
. 2020 Jul 10:ciaa953. doi: 10.1093/cid/ciaa953

Natural transmission of bat-like SARS-CoV-2ΔPRRA variants in COVID-19 patients

Yik Chun Wong 1,2, Siu Ying Lau 2,3, Kelvin Kai Wang To 2,3,4,5, Bobo Wing Yee Mok 2,3, Xin Li 1,2, Pui Wang 2,3, Shaofeng Deng 2,3, Kin Fai Woo 1,2, Zhenglong Du 1,2, Cun Li 2, Jie Zhou 2,3, Jasper Fuk Woo Chan 2,3,4,5, Kwok Yung Yuen 2,3,4,5, Honglin Chen 2,3,4, Zhiwei Chen 1,2,3,4,
PMCID: PMC7454488  PMID: 32649739

Abstract

Background

SARS-CoV-2 contains the furin cleavage PRRA motif in the S1/S2 region, which enhances viral pathogenicity but is absent in closely related bat and pangolin coronaviruses. It remains unknown if bat-like coronaviral variants without PRRA (ΔPRRA) can establish natural infection in humans.

Methods

Here, we developed a duplex digital PCR assay to examine ΔPRRA variants in Vero-E6-propagated isolates, human organoids, experimentally infected hamsters and COVID-19 patients.

Results

We found that currently transmitting SARS-CoV-2 contained a quasispecies of wildtype, ΔPRRA variants and upstream variants that have mutations upstream the PRRA motif. Moreover, the ΔPRRA variants were readily detected despite at a low intra-host frequency in transmitted founder viruses in hamsters and in COVID-19 patients including acute cases and a family cluster with a prevalence rate of 52.9%.

Conclusions

Our findings demonstrate that bat-like SARS-CoV-2ΔPRRA not only naturally exists but remains transmissible in COVID-19 patients, which have significant implications to zoonotic origin and natural evolution of SARS-CoV-2.

Keywords: COVID-19, SARS-CoV-2, viral variants, transmission, furin cleavage PRRA motif


Articles from Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America are provided here courtesy of Oxford University Press

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