A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein

M. Gordon Joyce; Rajeshwer S. Sankhala; Wei-Hung Chen; Misook Choe; Hongjun Bai; Agnes Hajduczki; Lianying Yan; Spencer L. Sterling; Caroline E. Peterson; Ethan C. Green; Clayton Smith; Natalia de Val; Mihret Amare; Paul Scott; Eric D. Laing; Christopher C. Broder; Morgane Rolland; Nelson L. Michael; Kayvon Modjarrad

SARS-CoV-2 has a likely zoonotic origin and horseshoe bats have been implicated as natural reservoirs of both SARS-CoV and SARS-CoV-2 (Menachery et al., 2015; Zhou et al., 2020) . As such, we next explored antibody cross-reactivity with the S glycoproteins of two bat SARS-related CoVs: SARSr-CoV Rs4874 (Ge et al., 2013; Yang et al., 2015) and Rs4231 (Hu et al., 2017) , which are closely related to a CC0 license. author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under The copyright holder for this preprint (which was not peer-reviewed) is the . https: //doi.org/10.1101 //doi.org/10. /2020 the progenitor of SARS-CoV and retain the ability to utilize human ACE-2. CR3022 was able to recognize a recombinant Spike glycoproteins generated from bat SARSr-CoV Rs4874, while 240CD, and other mouse generated monoclonal antibodies have a mixed recognition phenotype ( Figure 2F ).