In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 1 ( 2023-1-26), p. e1011131-
Abstract:
The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo . These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011131
DOI:
10.1371/journal.ppat.1011131.g001
DOI:
10.1371/journal.ppat.1011131.g002
DOI:
10.1371/journal.ppat.1011131.g003
DOI:
10.1371/journal.ppat.1011131.g004
DOI:
10.1371/journal.ppat.1011131.g005
DOI:
10.1371/journal.ppat.1011131.g006
DOI:
10.1371/journal.ppat.1011131.s001
DOI:
10.1371/journal.ppat.1011131.s002
DOI:
10.1371/journal.ppat.1011131.s003
DOI:
10.1371/journal.ppat.1011131.s004
DOI:
10.1371/journal.ppat.1011131.s005
DOI:
10.1371/journal.ppat.1011131.s006
DOI:
10.1371/journal.ppat.1011131.s007
DOI:
10.1371/journal.ppat.1011131.s008
DOI:
10.1371/journal.ppat.1011131.s009
DOI:
10.1371/journal.ppat.1011131.s010
DOI:
10.1371/journal.ppat.1011131.s011
DOI:
10.1371/journal.ppat.1011131.r001
DOI:
10.1371/journal.ppat.1011131.r002
DOI:
10.1371/journal.ppat.1011131.r003
DOI:
10.1371/journal.ppat.1011131.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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