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

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


    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 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



    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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