Evaluating the antiviral role of thapsigargin against respiratory syncytial virus and influenza A virus
Publication Date
December 31, 2025
Creator
Abstract
Respiratory syncytial virus (RSV) and influenza A virus (IAV) represent significant global health threats, exacerbated by their ability to co-infect hosts and evade immune responses. Current antiviral treatments are limited by specificity, resistance development, and variable efficacy in co-infection scenarios. This thesis investigates the potential of thapsigargin (TG) as a broad-spectrum antiviral agent targeting RSV, IAV, and their co-infections. TG demonstrated potent inhibition of viral replication across diverse cell models, including immortalised lines and
primary human bronchial epithelial cells, with reductions in viral titres exceeding 85% at non-cytotoxic concentrations.
Mechanistically, TG disrupts calcium homeostasis by inhibiting the SERCA pump, triggering endoplasmic reticulum stress and activating the unfolded protein response (UPR). This state induces antiviral pathways, limiting viral protein synthesis and enhancing innate immune signalling. Notably, TG established a prolonged antiviral effect,
maintaining efficacy for 48 hours post-treatment. In co-infection models, TG significantly reduced viral replication for both RSV and IAV.
TG’s host-centric approach offers advantages over conventional
antivirals, reducing the risk of resistance while providing broad-spectrum
efficacy. However, challenges remain, including variability in response
across cell types, potential off-target effects, and the need for extensive
in vivo validation. Future directions include optimising TG delivery methods, exploring combination therapies, and expanding its evaluation
to other RNA viruses. This work establishes TG as a promising antiviral
with implications for pandemic preparedness and respiratory disease
management, highlighting its potential to redefine the therapeutic
landscape against emerging viral threats.
Item Type
ethesis
Thesis Type
PhD
Supervisors
Subjects (LC)
Associated Schools / Departments
School of Veterinary Medicine and Science
Author URL(s)
eprints ID
81850
UoN Repository URI
Except where otherwise noted, this item's license is described as
File(s)![Thumbnail Image]()
Name
Evaluating the antiviral role of thapsigargin against respiratory syncytial virus and influenza A virus.pdf
Type
Full-text
Description
Examined. Corrections following viva
Size
4.73 MB
Format
Adobe PDF
Checksum (MD5)
32273091371586b94299160018b2800c