Yik Chun Wong1,2, Siu Ying Lau2,3, Kelvin Kai Wang To2,3,4,5, Bobo Wing Yee Mok2,3, Xin Li1,2, Pui Wang2,3, Shaofeng Deng2,3, Kin Fai Woo1,2, Zhenglong Du1,2, Cun Li2, Jie Zhou2,3, Jasper Fuk Woo Chan2,3,4,5, Kwok Yung Yuen2,3,4,5, Honglin Chen2,3,4, Zhiwei Chen1,2,3. 1. AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. 2. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. 3. State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. 4. Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China. 5. Department of Clinical Microbiology and Infection, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China.
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.
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-19patients, 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-19patients, which has significant implications regarding the zoonotic origin and natural evolution of SARS-CoV-2.
Authors: Brenda Martínez-González; María Eugenia Soria; Lucía Vázquez-Sirvent; Cristina Ferrer-Orta; Rebeca Lobo-Vega; Pablo Mínguez; Lorena de la Fuente; Carlos Llorens; Beatriz Soriano; Ricardo Ramos-Ruíz; Marta Cortón; Rosario López-Rodríguez; Carlos García-Crespo; Pilar Somovilla; Antoni Durán-Pastor; Isabel Gallego; Ana Isabel de Ávila; Soledad Delgado; Federico Morán; Cecilio López-Galíndez; Jordi Gómez; Luis Enjuanes; Llanos Salar-Vidal; Mario Esteban-Muñoz; Jaime Esteban; Ricardo Fernández-Roblas; Ignacio Gadea; Carmen Ayuso; Javier Ruíz-Hornillos; Nuria Verdaguer; Esteban Domingo; Celia Perales Journal: Pathogens Date: 2022-06-08
Authors: Mart M Lamers; Anna Z Mykytyn; Tim I Breugem; Yiquan Wang; Douglas C Wu; Samra Riesebosch; Petra B van den Doel; Debby Schipper; Theo Bestebroer; Nicholas C Wu; Bart L Haagmans Journal: Elife Date: 2021-04-09 Impact factor: 8.140
Authors: Niharika Gupta; Shine Augustine; Tarun Narayan; Alan O'Riordan; Asmita Das; D Kumar; John H T Luong; Bansi D Malhotra Journal: Biosensors (Basel) Date: 2021-05-01