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Determination of Coronavirus

CoV-2 S trimer in the pre-fusion conformation

Receptor Binding Mechanisms

was revealed by Wrapp et al. where they showed

and Cross-Reactivity

that while the overall structure of SARS CoV-2 S

The 2019-nCoV or SARS CoV-2 Shares genetic

protein was mostly similar to SARS-CoV S,

and morphologic features with other coronavirus

differences existed between the down

families, particularly from the betacoronavirus

conformations at the RBD12.

genus (SARS-CoV 2003). SARS CoV-2 makes use of

Another cryo-EM structure of SARS CoV-2 Spike

a glycosylated, homotrimeric class I fusion spike

glyco-protein complex resolved by Walls et al.

(S) protein to gain entry into host cells via the

showed that that the SARS-CoV-2 S glycoprotein

human angiotensin converting enzyme-2 (ACE2)

harbors a furin cleavage site at the boundary

receptor19. The SARS CoV-2 S glyco- protein bears

between the S1/S2 subunits, which is processed

significant structural homology with SARS-CoV

during biogenesis and differentiates this virus apart

compared to other major coronaviruses such as

from SARS-CoV and other SARS-related CoVs10.

the MERS-CoV.

Using Octet® binding assays, they showed that

The S-protein is known to exist in a metastable

the receptor-binding domains of SARS-CoV-2 S

pre-fusion conformation that undergoes

and SARS-CoV S engaged the human ACE2 with

rearrangements to fuse the viral membrane with

similar binding affinities. Similar observations were

the host cell membrane. Binding of the S1 subunit

reported by Joyce et al. using a high-resolution

to host-cell receptors triggers destabilization of

crystal structure of the SARS-CoV-2 S RBD5.

the pre-fusion trimer and conformational change

Additionally, in this work antibodies that were

in the protein initiates fusion with the host cell

known to interact with SARS-CoV and MERS CoV

membrane through the S2 subunit. In order to

receptor binding domains (RBD) were tested

engage the host-cell receptor, the receptor-

for SARS-CoV-2 binding activity using an Octet®

binding domain (RBD) of S1 would need to

kinetic assay. Only two antibodies, 240CD and

undergo hinge-like transitions that either hides

CR3022 out of the pool, displayed low nanomolar

or displays the receptor-binding regions which

binding affinities against the SARS-CoV 2 RBD.

are termed as down and up conformations

These two antibodies, however, competed

respectively, providing accessibility to receptor-

for the same SARS-CoV-2 RBD binding site

binding and presenting itself as a key antigenic

according to an Octet® cross-competition assay.

target for vaccine development.

Cross-competition or epitope binning assays

One of the first CryoEM structures of the SARS

can be used to segment monoclonal antibodies

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