MAUGI: Microarray for Universal Glycan Identification Based Upon Multiplexed Synthetic

Abstract

Enveloped viruses (EnV) are viruses that contain a lipid bilayer coating that is densely decorated with glycoproteins, and EnV include viruses that pose the greatest threat to human health, such as SARS-CoV-2, Ebola, Zika, Hendra, and Nipah viruses, and many, many others. Early, accurate, and facile identification of EnV that cause disease is critical to mitigating the threat of viruses and altering the course of the outbreak to achieve the best outcome. A challenge to early detection at remote locations or at the site of a new outbreak is that viral identification requires sophisticated laboratories, expensive equipment, and long delays, which can result in poorer outcomes as viral identification is delayed. Thus, there is a need for new approaches for identifying viruses that can be deployed rapidly, onsite, and that can accurately discriminate between different viruses. To address this challenge, we propose a new type of virus-binding microarray that relies on a novel class of biological recognition element that has been co-developed by the PIs Ð synthetic carbohydrate receptors (SCRs) Ð that bind to envelope glycans. As each EnV displays unique envelope glycans, the binding profiles of the different viruses to the different SCRs will vary, and EnV viruses will be identified based upon differences in their binding to the array. This project will develop the fundamental knowledge necessary to build such arrays, with a focus on the following three themes: (i) synthesizing a series of new SCRs with diverse binding profiles and that can be immobilized onto a microarray, (ii) use Hypersurface Photolithography to develop methods for patterning the SCR-functionalized glycan-binding polymer brush features within the microarray and with precise control over feature height and valency, and (iii) study binding experimentally and computationally between the SCR microarrays and biologically-relevant glycans as well as pseudotyped virus particles that recapitulate the envelope glycosylation of live EnV. Taken together, these studies will provide the fundamental understanding needed to create universal viral detection platforms Ð sensors that can identify an unknown EnV from a biological sample, rapidly, onsite at remote locations, and without complex equipment. This work addresses pressing Department of Defense needs related to protecting warfighter health and battlefield preparedness as well as minimizing national security risks related to viral outbreaks. An additional focus of the project is to provide research opportunities for students from traditionally underrepresented groups, who, by participating in the research, will receive training in cuttingedge science as well as counseling and guidance on how to prepare for careers in STEM disciplines.

Document Details

Document Type
DoD Grant Award
Publication Date
May 24, 2023
Source ID
W911NF2310234

Entities

People

  • Adam B Braunschweig

Organizations

  • Army Contracting Command
  • Hunter College
  • Office of the Secretary of Defense

Tags

Readers

  • Infectious Disease/Epidemiology
  • Military Science and Technology Research and Modernization.
  • Molecular and Cellular Biochemistry