Accession PRJCA014248
Title In vivo structural characterization of the SARS-CoV-2 RNA genome identifies host proteins vulnerable to repurposed drugs
Relevance Medical
Data types Raw sequence reads
Organisms Severe acute respiratory syndrome coronavirus 2
Middle East respiratory syndrome-related coronavirus
Severe acute respiratory syndrome-related coronavirus
Homo sapiens
Description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding of the RNA virus and its interactions with host proteins could improve therapeutic interventions for COVID-19. By using icSHAPE, we determined the structural landscape of SARS-CoV-2 RNA in infected human cells and from refolded RNAs, as well as the regulatory untranslated regions of SARS-CoV-2 and six other coronaviruses. We validated several structural elements predicted in silico and discovered structural features that affect the translation and abundance of subgenomic viral RNAs in cells. The structural data informed a deep-learning tool to predict 42 host proteins that bind to SARS-CoV-2 RNA. Strikingly, antisense oligonucleotides targeting the structural elements and FDA-approved drugs inhibiting the SARS-CoV-2 RNA binding proteins dramatically reduced SARS-CoV-2 infection in cells derived from human liver and lung tumors. Our findings thus shed light on coronavirus and reveal multiple candidate therapeutics for COVID-19 treatment.
Sample scope Monoisolate
Release date 2023-01-16
Publication
PubMed ID Article title Journal name DOI Year
33636127 In vivo structural characterization of the SARS-CoV-2 RNA genome identifies host proteins vulnerable to repurposed drugs Cell 10.1016/j.cell.2021.02.008 2021
Grants
Agency program Grant ID Grant title
Ministry of Science and Technology of the People's Republic of China (MOST) National Key Technologies R&D Program 2018YFA0107600 Heterogeneity of the fate decision of pluripotent stem cells and post-transcriptional regulation of early embryogenesis
Ministry of Science and Technology of the People's Republic of China (MOST) National Key Technologies R&D Program 2019YFA0110000
Accessions in other database
Accession Database name
GSE153984 NCBI
Submitter Qiangfeng  Cliff  Zhang  (qczhang@tsinghua.edu.cn)
Organization Tsinghua University
Submission date 2023-01-05

Project Data

Resource name Description
BioSample (22)  show -
GSA (1) -
CRA009460 RNA secondary structure of SARS-CoV-2 and other 6 virus in the UTR regions