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O-36 - DEFUSE proposed inserting field-sampled bat spike proteins into WIV1-SHC014 backbones and infecting humanized (hACE2) mice to assess SARS-like disease capacity

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type
observation
id
O-36
statement
In Thrust Area 1 the proposal planned to sequence and reverse-engineer spike proteins from newly-sampled bat SARSr-CoVs, insert them into bat-SARSr-CoV (WIV1, SHC014) backbones, and use the resulting chimeric viruses to infect humanized (hACE2-transgenic) mice and assess their capacity to cause SARS-like disease.
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linked
source
S-65 - Project DEFUSE proposal (EcoHealth Alliance to DARPA, 2018)
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Executive Summary — Technical Approach (TA1); TA1 in vivo pathogenesis
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quote
We will sequence their spike proteins, reverse engineer them to conduct binding assays, and insert them into bat SARSr-CoV (WIV1, SHC014) backbones... to infect humanized mice and assess capacity to cause SARS-like disease.

The core proposed gain-of-function-style activity: constructing chimeric bat coronaviruses and testing their human-disease potential in hACE2 mice. (Quote reconciled from degraded OCR of the scanned proposal.)

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