Transcriptome analysis of cepharanthine against a SARS-CoV-2-related coronavirus.

Shasha Li, Wenli Liu, Yangzhen Chen, Liqin Wang, Wenlin An, Xiaoping An, Lihua Song, Yigang Tong, Huahao Fan, Chenyang Lu
Author Information
  1. Shasha Li: Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology.
  2. Wenli Liu: Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology.
  3. Yangzhen Chen: College of Life Science and Technology, Beijing University of Chemical Technology.
  4. Liqin Wang: College of Life Science and Technology, Beijing University of Chemical Technology.
  5. Wenlin An: Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology.
  6. Xiaoping An: Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology.
  7. Lihua Song: Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology.
  8. Yigang Tong: Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology.
  9. Huahao Fan: Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology.
  10. Chenyang Lu: Department of Rheumatology and Immunology, West China Hospital, Sichuan University.

Abstract

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.

Keywords

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MeSH Term

Animals
Antiviral Agents
Benzylisoquinolines
Chlorocebus aethiops
Homeostasis
Humans
SARS-CoV-2
Transcriptome
Vero Cells

Chemicals

Antiviral Agents
Benzylisoquinolines
cepharanthine