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Deprecated: Implicit conversion from float 296.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Clin+Infect+Dis 2021 ; 73 (2): e437-e444 Nephropedia Template TP
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Natural Transmission of Bat-like Severe Acute Respiratory Syndrome Coronavirus 2 Without Proline-Arginine-Arginine-Alanine Variants in Coronavirus Disease 2019 Patients #MMPMID32649739
Wong YC; Lau SY; Wang To KK; Mok BWY; Li X; Wang P; Deng S; Woo KF; Du Z; Li C; Zhou J; Chan JFW; Yuen KY; Chen H; Chen Z
Clin Infect Dis 2021[Jul]; 73 (2): e437-e444 PMID32649739show ga
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains the furin cleavage Proline-Arginine-Arginine-Alanine (PRRA) motif in the S1/S2 region, which enhances viral pathogenicity but is absent in closely related bat and pangolin coronaviruses. Whether bat-like coronaviral variants without PRRA (?PRRA) can establish natural infections in humans is unknown. METHODS: Here, we developed a duplex digital polymerase chain reaction assay to examine ?PRRA variants in Vero-E6-propagated isolates, human organoids, experimentally infected hamsters, and coronavirus disease 2019 (COVID-19) patients. RESULTS: We found that SARS-CoV-2, as currently transmitting in humans, contained a quasispecies of wild-type, ?PRRA variants and variants that have mutations upstream of the PRRA motif. Moreover, the ?PRRA variants were readily detected despite being at a low intra-host frequency in transmitted founder viruses in hamsters and in COVID-19 patients, including in acute cases and a family cluster, with a prevalence rate of 52.9%. CONCLUSIONS: Our findings demonstrate that bat-like SARS-CoV-2DeltaPRRA not only naturally exists but remains transmissible in COVID-19 patients, which has significant implications regarding the zoonotic origin and natural evolution of SARS-CoV-2.