With this award, the Biomaterials Program in the Division of Materials Research and the Chemistry of Life Processes Program in the Division of Chemistry are funding Dr. Jessica R. Kramer from The University of Utah to study the role of mucus composition in coronavirus (COV) transmission. COV-related diseases have emerged as a serious public health threat. Airborne droplets from an infected person’s cough, sneeze, or even talking are a major source of viral spread. These droplets stem from virus-laden mucosalivary fluid and land on the mucus membranes of the next potential host (mouth, airway, eyes) or on hard surfaces. There, the virus is dispersed for the next infection. Mucus is produced in hundreds of forms that vary between species, and even person-to-person. The forms present could affect how easily the viruses pass through the mucus membrane, especially since some types bind directly to COVs. Mucus forms could also affect the concentration and viability of COVs in airborne droplets. The goal of this project is to identify the forms of mucus that result in increased airborne COV transmission and infection. This will be accomplished by simulation of cough droplets produced from varied mucus and using human cells coated with varied mucus. This knowledge could lead to development of new therapeutics that disrupt COV-mucus binding, or identify populations more vulnerable to COV transmission and infection.
Project Technical Abstract
This research project undertakes study of the role of mucin glycoprotein structures in coronavirus (COV) transmission via airborne particles, fomite objects, and in cellular entry through the glycocalyx. Epithelial tissue is coated with protective mucins that are secreted to form mucus and also tethered to the cell surface to form the glycocalyx. COVs must traverse these layers before entry into host cells for replication. Viral transmission through expelled airborne mucosalivary droplets is a major mode of transmission. Mucins are produced with a variety of attached glycans specific to each host. These glycans alter the viscoelasticity of mucosalivary fluid and directly bind to COV spike proteins. These factors could affect virus loading and viability in airborne particles and could affect docking and diffusion at the cell surface. However, such questions have been challenging to answer because native mucin glycosylation is poorly-defined and not tunable by current biological methods. The PI’s lab will synthesize mucin analogs with tunable COV-binding glycan patterns and will use them to engineer the glycocalyx of live cell surfaces. Coughs will be simulated and the role of mucin structure in airborne respiratory droplet COV transmission will be examined by characterization of droplet morphology, and viral loading and viability. Docking and diffusion at the cell surface, as well as replication, will be quantified on live epithelial cells.
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.
