Related Experiment Video

Updated: Nov 11, 2025

Production of a SARS-CoV-2 Virus-Like-Particle System to Investigate Viral Life Cycles In Vitro
09:26

Production of a SARS-CoV-2 Virus-Like-Particle System to Investigate Viral Life Cycles In Vitro

Published on: June 6, 2025

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Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and

Jin-Gu Lee1,2, Weiliang Huang3, Hangnoh Lee1,2

  • 1Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Cell & Bioscience
|March 26, 2021
PubMed
Abstract

Insights

SARS-CoV-2 Orf6 protein is highly pathogenic, interacting with host proteins to cause cell damage. A drug, Selinexor, can inhibit this interaction, reducing COVID-19 related cytotoxicity.

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19 with diverse clinical presentations.
  • The precise mechanisms of SARS-CoV-2 pathogenicity and host cell damage are not fully understood.
  • Identifying viral proteins responsible for cytotoxicity is crucial for understanding COVID-19 pathogenesis.

Purpose of the Study:

  • To identify SARS-CoV-2 pathogenic proteins responsible for COVID-19 symptomatology.
  • To investigate the host-pathogen interactions mediated by these viral proteins.
  • To explore potential therapeutic strategies targeting these interactions.

Main Methods:

  • Cytotoxicity assays of individual SARS-CoV-2 proteins in HEK 293T cells.
  • Subcellular localization studies of viral proteins in COS-7 cells.
  • Mass spectrometry-based affinity purification to identify host proteins interacting with SARS-CoV-2 Orf6.
  • In vitro testing of a drug (Selinexor) to inhibit Orf6-host protein interactions.

Main Results:

  • SARS-CoV-2 Orf6, Nsp6, and Orf7a proteins demonstrated significant cytotoxicity.
  • Orf6 protein, highly cytotoxic, localized to endoplasmic reticulum, autophagosome, and lysosomal membranes.
  • Proteomics identified interactions between Orf6 and key nucleopore proteins (RAE1, XPO1, RANBP2, nucleoporins).
  • Selinexor treatment significantly reduced Orf6-induced cytotoxicity in human cells.

Conclusions:

  • SARS-CoV-2 Orf6 is identified as a major pathogenic protein.
  • Key host nucleopore proteins interacting with Orf6 were elucidated.
  • Selinexor shows promise as a therapeutic agent targeting Orf6-host interactions to mitigate COVID-19-related cellular damage.

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