Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions [article]

Yue Wan, Siwy Ling Yang, Louis DeFalco, Danielle E Anderson, Yu Zhang, Ashley J Aw, Su Ying Lim, Xin Ni Lim, Kiat Yee Tan, Tong Zhang, Tanu Chawla, Yan Su (+5 others)
2021 bioRxiv   pre-print
SARS-CoV-2 has emerged as a major threat to global public health, resulting in global societal and economic disruptions. Here, we investigate the intramolecular and intermolecular RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 virus in cells using high throughput structure probing on Illumina and Nanopore platforms. We identified twelve potentially functional structural elements within the SARS-CoV-2 genome, observed that identical sequences can fold into divergent structures
more » ... n different subgenomic RNAs, and that WT and Δ382 virus genomes can fold differently. Proximity ligation sequencing experiments identified hundreds of intramolecular and intermolecular pair-wise interactions within the virus genome and between virus and host RNAs. SARS-CoV-2 binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2'-O-methylated. 2'-O-methylation sites in the virus genome are enriched in the untranslated regions and are associated with increased pair-wise interactions. SARS-CoV-2 infection results in a global decrease of 2'-O-methylation sites on host mRNAs, suggesting that binding to snoRNAs could be a pro-viral mechanism to sequester methylation machinery from host RNAs towards the virus genome. Collectively, these studies deepen our understanding of the molecular basis of SARS-CoV-2 pathogenicity, cellular factors important during infection and provide a platform for targeted therapy.
doi:10.1101/2021.01.17.427000 fatcat:xfeqeczj4ndl5fcbk5iv2mfuhu