Exportin 1 inhibition as antiviral therapy

• Published in: Drug discovery today Vol. 25; no. 10; pp. 1775 - 1781
• Main Authors: Uddin, Md. Hafiz, Zonder, Jeffrey A., Azmi, Asfar S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2020
• Subjects: Active Transport, Cell Nucleus; Animals; Antiviral Agents - therapeutic use; Cell Nucleus - drug effects; Cell Nucleus - immunology; Cell Nucleus - metabolism; Cell Nucleus - virology; COVID-19 - immunology; COVID-19 - metabolism; COVID-19 - virology; COVID-19 Drug Treatment; Drug Design; Exportin 1 Protein; Host-Pathogen Interactions; Humans; Karyopherins - antagonists & inhibitors; Karyopherins - metabolism; Molecular Targeted Therapy; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Receptors, Cytoplasmic and Nuclear - metabolism; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2020.06.014

•Nucleo-cytoplasmic transport is crucial for the proper functioning of cells.•Studies targeting nucleo-cytoplasmic transport have chiefly focused on cancer.•XPO1 mediated protein or RNA export is necessary for viral replication.•XPO1 contributes to the immunopathology by activating inflammatory signaling.•Inhibition of nuclear export using SINE may have broad-spectrum antiviral effect. Coronavirus 2019 (COVID-19; caused by Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2) is a currently global health problem. Previous studies showed that blocking nucleocytoplasmic transport with exportin 1 (XPO1) inhibitors originally developed as anticancer drugs can quarantine key viral accessory proteins and genomic materials in the nucleus of host cell and reduce virus replication and immunopathogenicity. These observations support the concept of the inhibition of nuclear export as an effective strategy against an array of viruses, including influenza A, B, and SARS-CoV. Clinical studies using the XPO1 inhibitor selinexor as a therapy for COVID-19 infection are in progress.