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Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19

Aditi Banerjee1, Steven J Czinn1, Russel J Reiter2

  • 1Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Life Sciences
|May 27, 2020
PubMed

Insights

This review explores how SARS-CoV-2 proteins cause endoplasmic reticulum (ER) stress. It suggests combining melatonin and andrographolide may offer a novel COVID-19 treatment by modulating ER stress and viral activity.

Area of Science:

  • Virology
  • Molecular Biology
  • Pharmacology

Background:

  • COVID-19, caused by SARS-CoV-2, necessitates understanding its mechanisms and treatments.
  • Viral infections, including SARS-CoV, induce endoplasmic reticulum (ER) stress and reactive oxygen species.
  • Current COVID-19 treatments have limitations, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

  • To review the role of viral proteins in activating ER stress pathways during SARS-CoV-2 infection.
  • To evaluate potential combination therapies for COVID-19, focusing on ER stress modulation.
  • To explore the therapeutic potential of melatonin and andrographolide for COVID-19.

Main Methods:

  • Literature review of viral protein involvement in ER stress.
  • Analysis of ER stress transducers (IRE-1, PERK, ATF-6) and downstream signaling pathways.
  • Evaluation of melatonin and andrographolide properties and computational docking studies.

Main Results:

  • SARS-CoV-2 proteins exploit host cell machinery, leading to ER stress.
  • Melatonin exhibits immunoregulatory, antioxidant, and ER stress-modulating properties beneficial for viral infections.
  • Andrographolide possesses immunomodulatory activity and computational studies suggest it binds to the SARS-CoV-2 binding site.

Conclusions:

  • The combination of melatonin and andrographolide shows promise as a potential therapeutic strategy for COVID-19.
  • This combination may mitigate ER stress and viral pathogenesis through their combined anti-inflammatory, antioxidant, and antiviral effects.
  • Further research and clinical trials are warranted to validate this proposed combination therapy.
Keywords:
2019-nCov/SARS-CoV-2AndrographolideCOVID-19Endoplasmic reticulum stressMelatoninUnfolded protein response

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