The architecture of the SARS-CoV-2 RNA genome inside virion

作者：Changchang Cao, Zhaokui Cai, Xia Xiao, Jian Rao, Juan Chen, Naijing Hu, Minnan Yang, Xiaorui Xing, Yongle Wang, Manman Li, Bing Zhou, Xiangxi Wang, Jianwei Wang, Yuanchao Xue · 发表于：Nature Communications · 年份：2021 · DOI：10.1038/s41467-021-22785-x · 被引用次数：217 · 研究领域：SARS-CoV-2 and COVID-19 Research、Viral gastroenteritis research and epidemiology、Bacteriophages and microbial interactions

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.