Exportin 1 inhibition as antiviral therapy

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Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
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Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds

Published on: October 29, 2015

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Md Hafiz Uddin1, Jeffrey A Zonder1, Asfar S Azmi1

  • 1Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA.

Drug Discovery Today
|June 23, 2020
PubMed

Insights

Exportin 1 (XPO1) inhibitors, initially for cancer, show promise in blocking viral replication by trapping viral components in the host cell nucleus. Clinical trials are underway to evaluate XPO1 inhibitors for treating COVID-19 infections.

Area of Science:

  • Virology
  • Oncology
  • Cell Biology

Background:

  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the global health crisis, COVID-19.
  • Exportin 1 (XPO1) is a key protein involved in nucleocytoplasmic transport.
  • XPO1 inhibitors have been developed as anticancer agents.

Purpose of the Study:

  • To investigate the potential of inhibiting nuclear export as a therapeutic strategy against viral infections, including SARS-CoV-2.
  • To explore the repurposing of XPO1 inhibitors for treating COVID-19.

Main Methods:

  • Blocking nucleocytoplasmic transport using XPO1 inhibitors.
  • Quarantining viral accessory proteins and genomic materials within the host cell nucleus.
  • Evaluating the reduction in virus replication and immunopathogenicity.

Main Results:

  • Previous studies demonstrated that XPO1 inhibition can reduce replication and immunopathogenicity of various viruses.
  • Blocking XPO1 effectively sequesters viral components in the nucleus, limiting their spread.
  • XPO1 inhibitors show potential for broad-spectrum antiviral activity.

Conclusions:

  • Inhibition of nuclear export via XPO1 is a viable strategy against viral infections like SARS-CoV-2.
  • XPO1 inhibitors represent a promising therapeutic avenue for COVID-19.
  • Ongoing clinical studies are assessing the efficacy of selinexor, an XPO1 inhibitor, for COVID-19 treatment.

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