Date of Award
2026
Document Type
Open Access Dissertation
Degree Name
Doctor of Philosophy in Biological Sciences (PhD)
Administrative Home Department
Department of Biological Sciences
Advisor 1
Caryn L. Heldt
Advisor 2
Stephen M. Techtmann
Committee Member 1
Paul D. Goetsch
Committee Member 2
Jennifer Becker
Abstract
Virus inactivation depends on how antiviral agents interact with the virus itself. These interactions can disrupt the lipid envelope, destabilize the capsid, alter surface glycoproteins, promote aggregation, or interfere with how the virus binds to surfaces, ultimately causing a loss of infectivity. How a virus responds is closely tied to its structure. Non-enveloped viruses are generally more resistant because their protein capsids are highly robust, while enveloped viruses are often more vulnerable because their lipid membranes are easier to disrupt. At the same time, environmental factors such as pH, ionic strength, temperature, organic matter, and surface chemistry can strongly influence these outcomes by affecting both virion stability and virus–material interactions. Although antiviral materials and chemical inactivation methods are widely used, the mechanisms behind them are still not fully understood. This dissertation addresses that gap by examining virus–antiviral interactions from structural and biophysical perspectives, with the goal of understanding how viral architecture shapes susceptibility to antiviral treatment.
Using model enveloped and non-enveloped viruses, this dissertation explores antiviral mechanisms across material-based capture, surfactant-mediated inactivation, and nanoscale characterization. Cupric-modified phyllosilicate minerals were investigated as antiviral materials for high-touch surfaces and were found to remove virus primarily through binding rather than irreversible inactivation. Sustainable glucoside and amine oxide surfactants were then evaluated as alternatives to Triton X-100 for solvent–detergent viral inactivation, and several showed equal or greater efficacy against SuHV-1, HSV, and XMuLV. Structural studies further revealed that surfactant treatment produced distinct, virus-dependent responses, including aggregation, swelling-like morphological changes, and loss of infectivity without complete particle disruption. These findings highlight the central role of viral architecture in determining inactivation pathways. Finally, this dissertation shows that immobilization chemistry can substantially distort the apparent morphology of viruses and exosomes in surface-based analyses, emphasizing the need to account for analytical artifacts when interpreting nanoscale data. Overall, this work advances the mechanistic understanding of virus–antiviral interactions and provides insight for designing antiviral materials, more sustainable virus-clearance strategies, and more reliable structural characterization methods.
Recommended Citation
Sharma, Vaishali, "FROM SURFACES TO BIOTHERAPEUTICS: UNDERSTANDING THE MECHANISMS OF VIRUS INACTIVATION", Open Access Dissertation, Michigan Technological University, 2026.