Journal
BRIEFINGS IN BIOINFORMATICS
Volume 22, Issue 2, Pages 1378-1386Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bib/bbaa387
Keywords
SARS-CoV-2; COVID-19; GX_P2V; cellular stress; cepharanthine; transcriptome
Funding
- Key Project of Beijing University of Chemical Technology [XK1803-06]
- National Key Research and Development Program of China [2018YFA0903000, 2020YFC2005405, 2020YFA0712100, 2020YFC0840805]
- Funds for First-class Discipline Construction [XK1805]
- Inner Mongolia Key Research and Development Program [2019ZD006]
- National Natural Science Foundation of China [81672001, 81621005]
- NSFC-MFST project (China-Mongolia) [31961143024]
- Fundamental Research Funds for Central Universities [BUCTRC201917, BUCTZY2022]
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This study identified cepharanthine (CEP) as an effective antiviral agent against a SARS-CoV-2-related virus, reversing dysregulated genes and pathways associated with cellular stress response and heat shock response. Single-cell transcriptomes analysis also showed enrichment of genes related to cellular stress responses and autophagy pathways in peripheral blood mononuclear cells from COVID-19 patients.
Antiviral therapies targeting the pandemic coronavirus disease 2019 (COVID-19) are urgently required. We studied an already-approved botanical drug cepharanthine (CEP) in a cell culture model of GX_P2V, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related virus. RNA-sequencing results showed the virus perturbed the expression of multiple genes including those associated with cellular stress responses such as endoplasmic reticulum (ER) stress and heat shock factor 1 (HSF1)-mediated heat shock response, of which heat shock response-related genes and pathways were at the core. CEP was potent to reverse most dysregulated genes and pathways in infected cells including ER stress/unfolded protein response and HSF1-mediated heat shock response. Additionally, single-cell transcriptomes also confirmed that genes of cellular stress responses and autophagy pathways were enriched in several peripheral blood mononuclear cells populations from COVID-19 patients. In summary, this study uncovered the transcriptome of a SARS-CoV-2-related coronavirus infection model and anti-viral activities of CEP, providing evidence for CEP as a promising therapeutic option for SARS-CoV-2 infection.
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