Online Archive of University of Virginia Scholarship
Pushing the Envelope: Mathematical Modelling Approaches to Uncover Mechanisms of Viral Attachment and Fusion with Host Cell Membranes24 views
Author
Adenekan, Oyinkansola, Biomedical Engineering - School of Engineering and Applied Science, University of Virginia
Advisors
Kasson, Peter, Chemistry, Georgia Institute of Technology
Naegle, Kristen, Biomedical Engineering, University of Virginia
Abstract
Enveloped viruses like influenza and SARS-CoV-2 pose a significant public health burden. Thorough characterization of their entry mechanisms is critical for developing effective vaccines and therapeutics. Viral entry proceeds through two steps: attachment to the host cell membrane and fusion with it, both of which are driven by complex molecular interactions that remain incompletely understood. While experimental approaches have advanced our knowledge of these processes, they are limited in their ability to capture the dynamic mechanisms involved in entry. Mathematical and computational approaches which analyze experimental data and simulate molecular interactions can bridge these gaps. In this thesis, we use principles from statistical mechanics to advance two methods for studying viral entry. First, we analyze the kinetics of SARS-CoV-2 fusion from analysis of single-event fluorescence data, introducing hypoexponential functions for extracting reaction rate constants that vary across sequential reaction steps. This approach recovers more detailed kinetic information than existing methods that assume equal rates across steps. Second, we build upon previously developed dynamic simulations of viral binding to better understand the effect of membrane configuration on viral attachment. Using pair potentials derived from molecular dynamics simulations, we reproduce membrane patterning that reflects varying concentrations of the receptor GD1A and cholesterol. Together, these methods advance the methodological toolkit available for studying viral entry, contributing to the experimental-computational feedback loop essential for deepening our understanding of viral entry.
Adenekan, Oyinkansola. Pushing the Envelope: Mathematical Modelling Approaches to Uncover Mechanisms of Viral Attachment and Fusion with Host Cell Membranes. University of Virginia, Biomedical Engineering - School of Engineering and Applied Science, PHD (Doctor of Philosophy), 2026-07-22, https://doi.org/10.18130/vf70-4954.
