2. Academic Validation
  3. Pharmacological Manipulation of UPR: Potential Antiviral Strategy Against Chikungunya Virus

Pharmacological Manipulation of UPR: Potential Antiviral Strategy Against Chikungunya Virus

  • Indian J Microbiol. 2022 Dec;62(4):634-640. doi: 10.1007/s12088-022-01046-5.
Nishtha Agrawal 1 2,  Sanjesh Saini 1,  Madhu Khanna 1,  Gagan Dhawan 2 3 4,  Uma Dhawan 5
Affiliations

Affiliations

  • 1 Department of Virology (a Unit of Department of Microbiology), Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007 India.
  • 2 Department of Biomedical Science, Acharya Narendra Dev College, University of Delhi, Kalkaji, New Delhi, 110019 India.
  • 3 Delhi School of Skill Enhancement and Entrepreneurship Development, Institution of Eminence, University of Delhi, Delhi, 110007 India.
  • 4 School of Allied Medical Services, Delhi Skill and Entrepreneurship University, Sector-9, Dwarka, New Delhi, 110077 India.
  • 5 Department of Biomedical Science, Bhaskaracharya College of Applied Sciences, University of Delhi, Sector-2, Dwarka, New Delhi, 110075 India.
PMID: 36458214 DOI: 10.1007/s12088-022-01046-5
Abstract

Abstract: Viruses invade the host cells and maneuver the cellular translation machinery to translate the Viral Proteins in substantial amounts, which may disturb Endoplasmic Reticulum homeostasis leading to induction of Unfolded Protein Response (UPR), a host response pathway involved in viral pathogenesis. Here, we investigated the effect of UPR pathways on the pathogenesis of chikungunya virus Infection. We observed that chikungunya virus mediated the modulation of UPR. A positive modulation was observed in the activation of IRE1 and ATF6 branch while the PERK branch of UPR observed suppressed upon virus Infection. We further investigated the effect of the inhibition of UPR pathways on chikungunya virus replication using inhibitors for each branch. Cells treated with 3-ethoxy-5,6-dibromosalicylaldehyde (IRE1 Inhibitor) and AEBSF (ATF6 inhibitor) significantly inhibits the viral replication process. This study has provided a novel perspective in designing antivirals against chikungunya virus.

Supplementary information: The online version contains supplementary material available at 10.1007/s12088-022-01046-5.

Keywords

3-ethoxy-5,6-dibromosalicylaldehyde; AEBSF; Chikungunya virus; ER stress; Unfolded protein response; Virus replication.

Figures
Products