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Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions #MMPMID34433821
Yang SL; DeFalco L; Anderson DE; Zhang Y; Aw JGA; Lim SY; Lim XN; Tan KY; Zhang T; Chawla T; Su Y; Lezhava A; Merits A; Wang LF; Huber RG; Wan Y
Nat Commun 2021[Aug]; 12 (1): 5113 PMID34433821show ga
SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Delta382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different structures, and that WT and Delta382 virus genomes fold differently. Proximity ligation sequencing identify hundreds of RNA-RNA interactions within the virus genome and between the virus and host RNAs. SARS-CoV-2 genome binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2'-O-methylated. 2'-O-methylation sites are enriched in viral untranslated regions, associated with increased virus pair-wise interactions, and are decreased in host mRNAs upon virus infection, suggesting that the virus sequesters methylation machinery from host RNAs towards its genome. These studies deepen our understanding of the molecular and cellular basis of SARS-CoV-2 pathogenicity and provide a platform for targeted therapy.