Comprehensive in-vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms.

摘要: SARS-CoV-2 is the positive-sense RNA virus that causes COVID-19, a disease has triggered major human health and economic crisis. The genome of unique among viral RNAs in its vast potential to form stable structures yet, as much 97% 30 kilobases have not been structurally explored context infection. Our limited knowledge genomic architecture fundamental limitation both our mechanistic understanding coronavirus life cycle development COVID-19 RNA-based therapeutics. Here, we apply novel long amplicon strategy determine for first time secondary structure probed infected cells. In addition conserved structural motifs at termini, report new features like conformationally flexible programmed ribosomal frameshifting pseudoknot, host structures, each which highlights importance studying their native context. in-depth analysis reveals extensive networks well-folded throughout Orf1ab aspects distinguish it from other single-stranded, viruses. Evolutionary shows several are across beta coronaviruses pinpoint individual regions merit downstream functional analysis. native, complete SAR-CoV-2 presented here roadmap will facilitate focused studies on mechanisms replication, translation packaging, guide identification drug targets against COVID-19.