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Preda, Cristian Alexandru (2025) Evaluating the antiviral role of thapsigargin against respiratory syncytial virus and influenza A virus. PhD thesis, University of Nottingham.

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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:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Mellits, Ken Goulding, Leah
Keywords:	Thapsigargin; Antiviral agent; Respiratory disease management
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Related URLs:	URL URL Type https://www.mdpi.com/1999-4915/13/2/234 Author
Item ID:	81850
Depositing User:	Preda, Cristian
Date Deposited:	31 Dec 2025 04:40
Last Modified:	31 Dec 2025 04:40
URI:	https://eprints.nottingham.ac.uk/id/eprint/81850

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