Virucidal materials: From synthesis to function

Abstract

Currently, there are over 219 species of viruses known to infect human beings, with new pathogenic viruses emerging regularly and expected to become more frequent. At the time of writing, the world was suffering from the burden of the COVID-19 global pandemic. Despite the increasing number of pathogenic viruses, the antiviral therapies in clinical use are extremely limited. Of these, the majority are intracellular, virus-specific, and prone to the development of resistance limiting their utility for new epidemics and pandemics. Recently, a seminal study into the development of non-toxic broad-spectrum virucidal antivirals has brought the prospect of such materials more to the forefront and encouraged further research such as that performed within this thesis. However, the development of such materials is not easy and learning into the parameters leading to virucidal activity is ongoing. The aim of this project was to take forward the principles which lead to the development of the non-toxic virucidal materials and use the principles to covert known, well-published non-toxic entry inhibitors (cell surface receptor analogues) into virucidal materials looking towards human therapeutic use. To this end, there were 16 antivirals which were tested within this project, the majority of which were developed for the project. Of these, four were found to be virucidal. The project also includes an investigation into the effect of different cores and ligand lengths on antiviral activity and mechanism. Through this, it was found that the core type plays a vital role in achieving a virucidal mechanism of action. The effect of ligand length was found to be more ambiguous but still likely to affect whether a virucidal mechanism is achieved. It is believed that the development approach described here can be applied to various well-published non-toxic antiviral materials, such as heparin, to improve their efficacy, create a virucidal mechanism, and make them more clinically relevant for the treatment of viral infections.

Date of Award	31 Dec 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Samuel Jones (Supervisor) & Sarah Cartmell (Supervisor)