Related Experiment Video

Updated: Sep 30, 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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Free ISG15 and Protein ISGylation Emerging in SARS-CoV-2 Infection

Angeles C Tecalco Cruz1

  • 1Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México (UACM), CDMX, México.

Current Drug Targets
|March 17, 2022
PubMed

Insights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease PLpro removes ISG15, impacting host antiviral defenses. Developing SARS-CoV-2-PLpro inhibitors may restore immune responses against COVID-19.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Interferon-simulated gene 15 (ISG15) is a ubiquitin-like protein involved in antiviral and immune responses.
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes proteases for viral replication, crucial for COVID-19 progression.

Purpose of the Study:

  • To discuss the role of ISG15 and ISGylation in the context of SARS-CoV-2 infection.
  • To explore the implications of SARS-CoV-2 protease PLpro in deISGylating host proteins and its effect on immune evasion.
  • To highlight the potential of developing SARS-CoV-2-PLpro inhibitors for therapeutic strategies.

Main Methods:

  • Literature review and discussion of existing research on ISG15, ISGylation, and SARS-CoV-2.
  • Analysis of the mechanism by which SARS-CoV-2 PLpro interacts with and modifies ISGylated proteins.
  • Exploration of the functional consequences of ISG15 removal on host antiviral pathways.

Main Results:

  • SARS-CoV-2 PLpro effectively removes ISG15 from host proteins like IRF3 and MDA5.
  • This deISGylation activity by SARS-CoV-2 PLpro impairs host immune and antiviral defenses.
  • ISG15 modification and its removal by viral proteases are critical factors in SARS-CoV-2 pathogenesis.

Conclusions:

  • ISG15 and ISGylation are key components of the host antiviral response targeted by SARS-CoV-2.
  • Inhibition of SARS-CoV-2 PLpro activity presents a promising therapeutic avenue to restore host immunity against COVID-19.
  • Further research into ISG15-PLpro interactions can lead to novel strategies for combating SARS-CoV-2 infection.
Keywords:
COVID-19ISG15ISGylationSARS-CoV-2SCoV-PLproprotease

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