EAGER: SARS-CoV-2 Pseudovirus via a novel eukaryotic construction in yeast

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One of the significant impediments in the fight against a disease like COVID-19 is the availability of a safe and effective mimic of the SARS-CoV-2 virus that could be used without the need of very specialized handling and laboratory equipment that could serve as early-stage substitute during technology development. As an early stage substitute the SARS-CoV-2 mimic, or pseudovirus, could serve as a safe, effective tool to create antibodies, develop purification methods, design vaccine candidates, and build diagnostic kits. In the absence of suitable mimics, the nationwide ability to quickly pass/fail ideas is vastly limited. In particular, due to the low number of facilities that are able to safely handle an infectious agent, a strain on infrastructure occurs which ultimately limits the number of teams “in the fight” who may have significant expertise but minimal accommodations. This project will produce such a safe pseudovirus that could be widely used for the development of materials for this and potentially future pandemics. In addition, a postdoc will be trained in an interdisciplinary environment.The objective of this proposal is to develop a synthetic yeast construct that will serve as a safe (BSL-1), robust and reliable surrogate for SARS-CoV-2 or other infectious agents against which diagnostic and environmental testing assays could be developed and validated. The key elements of the proposed work are 1) the development of a yeast surface display platform in which the surface density of key proteins normally found on the surface of SARS-CoV-2 can be expressed, 2) the development of a robust production platform for the biomanufacturing of the yeast pseudovirus, and 3) the validation of the yeast pseudovirus against SARS-CoV-2 to demonstrate that the yeast pseudovirus can be used as a mimic for SARS-CoV-2 for the development of biologics.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.