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

Siwy Ling Yang, Louis DeFalco, Danielle E. Anderson, Yu Zhang, Jong Ghut Ashley Aw, Su Ying Lim, Xin Ni Lim, Kiat Yee Tan, Tong Zhang, Tanu Chawla, Yan Su, Alexander Lezhava, Andres Merits, Lin-Fa Wang (), Roland G. Huber () and Yue Wan ()
Additional contact information
Siwy Ling Yang: Agency for Science, Technology and Research (A*STAR)
Louis DeFalco: Agency for Science, Technology and Research (A*STAR), Matrix #07-01
Danielle E. Anderson: Programme in Emerging Infectious Diseases, Duke-NUS Medical School
Yu Zhang: Agency for Science, Technology and Research (A*STAR)
Jong Ghut Ashley Aw: Agency for Science, Technology and Research (A*STAR)
Su Ying Lim: Agency for Science, Technology and Research (A*STAR)
Xin Ni Lim: Agency for Science, Technology and Research (A*STAR)
Kiat Yee Tan: Agency for Science, Technology and Research (A*STAR)
Tong Zhang: Agency for Science, Technology and Research (A*STAR)
Tanu Chawla: Programme in Emerging Infectious Diseases, Duke-NUS Medical School
Yan Su: Agency for Science, Technology and Research (A*STAR)
Alexander Lezhava: Agency for Science, Technology and Research (A*STAR)
Andres Merits: Institute of Technology, University of Tartu
Lin-Fa Wang: Programme in Emerging Infectious Diseases, Duke-NUS Medical School
Roland G. Huber: Agency for Science, Technology and Research (A*STAR), Matrix #07-01
Yue Wan: Agency for Science, Technology and Research (A*STAR)

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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 (Δ382) 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 Δ382 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.

Date: 2021
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DOI: 10.1038/s41467-021-25357-1

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