ABSTRACT

NON-TECHNICAL SUMMARY

The health and economic devastation brought on by the Covid-19 pandemic underscores the urgent need to develop a multifaceted pandemic planning and response to stop viral outbreaks. This project takes a materials science and engineering approach to develop broad-spectrum antiviral materials that work against many viruses without inducing resistance. The research team has shown that a class of conjugated polymers and oligomers exhibit remarkable near-UV/visible light-activated killing of bacteriophages and the SARS-CoV-2 coronavirus that causes the Covid-19 pandemic; greater than 99.9999% viral inactivation is routinely achieved. This project focuses on elucidating the antiviral mechanism of the conjugated compounds. Propensity of the compounds to interact with and disrupt the structures and functions of several viral targets, including spike and capsid proteins, viral membrane, and RNA, will be studied using a suite of experimental techniques. Combined with computational simulations, a fundamental understanding of the interactions between the synthetic compounds with viral components that are responsible for their antiviral activity will be gained. Such insights will guide the rational design of new compounds with optimal antiviral properties to slow the spread of infections. This project will also identify virus components to target and degrade that will result in viral inactivation. Taken together, this project will contribute towards the development of highly effective and broad-spectrum antiviral materials for healthcare workers and for the public and will transform our ability to prepare for and respond to current and future outbreaks.

TECHNICAL SUMMARY

The goal of this project is to gain a fundamental understanding of the intermolecular interactions between novel synthetic conjugated polyelectrolyte polymers (CPEs) and oligomers (OPEs) with various viral assemblies that give rise to their remarkable light-activated broad-spectrum antiviral activity. CPEs and OPEs have recently been shown to be highly efficient at inactivating the SARS-CoV-2 virus that causes the Covid-19 pandemic. The proposed project focuses on elucidating the antiviral mechanism of the compounds with the ultimate goal of guiding the rational design of novel materials with optimal properties. The CPEs and OPEs are charged and amphiphilic in nature, which provides them the ability to interact with and potentially disrupt the structures, and thereby functions, of multiple virial targets. Additionally, light-activated photosensitizing activity of the compounds can further contribute to their antiviral efficacy. Specifically, the propensity of CPEs and OPEs with varying backbones, chain length, side and end groups, charge density and distribution to interact with and disrupt the structures and functions of several viral macromolecular assemblies, including protein assemblies, membranes, and nucleic acids. The multidisciplinary team will use a suite of biophysical and materials characterization methods to study the interactions between CPEs and OPEs and viral targets, from molecular structural scale to macroscopic property levels, combined synergistically with closely related simulations. Comparing our findings with functional assays and antiviral activities will enable us to elucidate the toxicity mechanism and structure-function relationship of these novel synthetic antiviral materials.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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