The architecture of the SARS-CoV-2 RNA genome inside virion.
Nat Commun, 2021/06/24;12(1):3917.
Cao C[1], Cai Z[1, 2], Xiao X[3], Rao J[3], Chen J[1], Hu N[1, 2], Yang M[4], Xing X[4], Wang Y[4], Li M[5], Zhou B[6, 7], Wang X[4], Wang J[8, 9], Xue Y[10, 11]
Affiliations
PMID: 34168138DOI: 10.1038/s41467-021-22785-x
Impact factor: 17.694
Abstract
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.
MeSH terms
Animals; COVID-19; Cells, Cultured; Chlorocebus aethiops; Genome, Viral; Humans; Nucleic Acid Conformation; RNA, Viral; SARS-CoV-2; Sequence Analysis, RNA; Virion
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