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Cao, Changchang; Cai, Zhaokui; Xiao, Xia; Rao, Jian; Chen, Juan; Hu, Naijing; Yang, Minnan; Xing, Xiaorui; Wang, Yongle; Li, Manman; Zhou, Bing; Wang, Xiangxi; Wang, Jianwei; Xue, Yuanchao
Nature communications, 06/2021, Letnik: 12, Številka: 1Journal Article
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.
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in: SICRIS
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