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Clin Infect Dis . Natural Transmission of Bat-Like SARS-CoV-2PRRA Variants in COVID-19 Patients

tetano

Editor, Senior Moderator
Clin Infect Dis


. 2020 Jul 10;ciaa953.
doi: 10.1093/cid/ciaa953. Online ahead of print.
Natural Transmission of Bat-Like SARS-CoV-2PRRA Variants in COVID-19 Patients


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



Affiliations

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; furin cleavage PRRA motif; transmission; viral variants.
 
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