SARS-CoV-2 carries the largest single-stranded RNA genome and is the causal pathogen of the ongoing COVID-19 pandemic. How the SARS-CoV-2 RNA genome is folded in the virion remains unknown. To fill the knowledge gap and facilitate structure-based drug development, we develop a virion RNA in situ conformation sequencing technology, named vRIC-seq, for probing viral RNA genome structure unbiasedly. Using vRIC-seq data, we reconstruct the tertiary structure of the SARS-CoV-2 genome and reveal a surprisingly “unentangled globule” conformation. We uncover many long-range duplexes and higher-order junctions, both of which are under purifying selections and contribute to the sequential package of the SARS-CoV-2 genome. Unexpectedly, the D614G and the other two accompanying mutations may remodel duplexes into more stable forms. Lastly, the structure-guided design of potent small interfering RNAs can obliterate the SARS-CoV-2 in Vero cells. Overall, our work provides a framework for studying the genome structure, function, and dynamics of emerging deadly RNA viruses. Secondary structures and long-range RNA interactions of the SARS-CoV-2 genome have been investigated by various sequencing methods. Here the authors use an RNA-RNA hybrid sequencing method to predict the secondary and tertiary structure of the SRAS-CoV-2 RNA genome in the virion.
【저자키워드】 SARS-CoV-2, Sequencing, Virus structures, 【초록키워드】 Structure, Mutation, knowledge, COVID-19 pandemic, RNA, pathogen, RNA viruses, D614G, predict, SRAS-CoV-2, Interaction, junctions, Vero cells, viral RNA genome, RNA genome, virion, forms, genome structure, secondary, single-stranded, sequencing technology, develop, investigated, facilitate, provide, contribute, sequencing method, the SARS-CoV-2, the SARS-CoV-2 genome, 【제목키워드】 RNA genome, virion, the SARS-CoV-2,