Natural Transmission of Bat-like Severe Acute Respiratory Syndrome Coronavirus 2 Without Proline-Arginine-Arginine-Alanine Variants in Coronavirus Disease 2019 Patients. (10th July 2020)

• Record Type: Journal Article
• Authors: Wong, Yik Chun; Lau, Siu Ying; Wang To, Kelvin Kai; Mok, Bobo Wing Yee; Li, Xin; Wang, Pui; Deng, Shaofeng; Woo, Kin Fai; Du, Zhenglong; Li, Cun; Zhou, Jie; Chan, Jasper Fuk Woo; Yuen, Kwok Yung; Chen, Honglin; Chen, Zhiwei
• Is Part Of: Clinical infectious diseases. Volume 73:Number 2(2021)
• Page Start: e437
• Page End: e444
• Publication Date: 2020-07-10
• Subjects: COVID-19 -- SARS-CoV-2 -- viral variants -- transmission -- furin cleavage PRRA motif; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa953
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: 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-2ΔPRRA 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. Abstract : Using a specific digital PCR assay, we discovered the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants carrying mutations upstream and at the S1/S2 site in COVID-19 patients. Bat-like SARS-CoV-2ΔPRRA variants naturally exist and remain transmissible in humans.