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The Veesler Lab Profile picture
@veeslerlab
Nov 1 • 6 tweets • 2 min read • Read on X
Excited to share our latest work elucidating the mechanisms of coronavirus entry into cells!

Led by @Dr_MattMcCallum on our side in collaboration with Huan Yan's lab (TaiKang Center for Life and Medical Sciences)



1/5nature.com/articles/s4158…
In 2019, we proposed w @coronalexington @axiong_x that coronavirus entry into cells involves a spike (S) molecular ratcheting mechanism & discovered that antibodies could functionally mimic the receptor by inducing these S conformational changes

2/5
cell.com/cell/fulltext/…
This movie made with @janetiwasa summarizes this ratcheting mechanism

3/5
In this manuscript, we dissect what makes a functional receptor from a mechanistic standpoint and shows that two key features to promote entry into cells are proper spatial/geometric organization & the ability to induce this ratcheting mechanism

4/5 Image
We found that even an antibody targeting the S N-terminal domain (S2L20) and preventing the receptor-binding domain from closing promotes S ratcheting and fusogenic triggering!

5/6 Image
Thank you to everyone involved and for reading!

6/6

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More from @veeslerlab

The Veesler Lab Profile picture
Jul 9
How many times did coronaviruses evolve the ability to use ACE2 as receptor for infection? Find out by reading this @biorxivpreprint in collab with Huan Yan (Wuhan Univ)

Led by Ma CB, Liu C @YoungjunPark11 Tang J & Chen J

@HHMINEWS
@UWBiochemistry

1/9
 biorxiv.org/content/10.110…
We previously described the unexpected discovery that MERS-related coronaviruses (MERSr-CoVs) discovered in African bats use ACE2 as receptor instead of the MERS-CoV receptor DPP4 (as described in this thread )



2/9
nature.com/articles/s4158…
It turns out that recently described MERSr-CoVs identified in European bats (MOW15-22 & PnNL2018B) with highly divergent receptor-binding motif (RBM) also use ACE2 but with a distinct and much narrower species tropism

3/9 Image
Read 9 tweets
The Veesler Lab Profile picture
Mar 14
A few months ago, we asked if imprinting impacts immune responses to the recently updated XBB.1.5 spike (S) #COVID19 booster? The peer-reviewed version of our manuscript is now available
@HHMINEWS @UWBiochemistry

1/11

cell.com/immunity/fullt…
The original thread describing our results is below


2/11
During the review process, we added data showing elicitation of broadly neutralizing polyclonal plasma antibodies (Abs) against a wider ranger of #SARSCoV2 variants (now including HK.3 and JN.1) and at a later time point (~50 days post XBB.1.5 booster vaccination)

3/11 Image
Read 11 tweets
The Veesler Lab Profile picture
Jan 10
Are you wondering how the human coronavirus HKU1 recognizes the TMPRSS2 host receptor?

Find out in our @biorxivpreprint led by
@Dr_MattMcCallum @YoungjunPark11

@HHMINEWS @UWBiochemistry

1/26
biorxiv.org/content/10.110…
HKU1 was discovered in 2005 from a patient with pneumonia (it was circulating for ≥10 years) and is endemic in humans. HKU1 is an embecovirus, a subgenus for which the entry process into cells is less well understood than for most other betaCoVs such as #SARSCoV2

2/26
Recently, @Virus_Immunity @JBuchrieser @virusfusion007 and colleagues showed that human TMPRSS2 is an entry receptor for HKU1

3/26

nature.com/articles/s4158…
Read 26 tweets
The Veesler Lab Profile picture
Dec 14, 2023
Can we design #COVID19 vaccines that are largely insensitive to viral evolution? Find out by reading our @biorxivpreprint preprint

Led by @0327jimin

@HHMINEWS @UWBiochemistry

1/22

biorxiv.org/content/10.110…
Coronavirus spike (S) glycoproteins comprise the S1 subunit, which mediates attachment to host receptor(s), and the S2 subunit (fusion machinery) that promotes fusion of the viral and host membranes to initiate infection

2/22 Image
The S2 subunit (fusion machinery) is much more conserved than the S1 subunit (comprising the RBD and NTD), and harbors several antigenic sites targeted by broadly neutralizing and protective monoclonal antibodies (Abs)

3/22
Read 22 tweets
The Veesler Lab Profile picture
Dec 1, 2023
Is imprinting impacting immune responses to the recently updated XBB.1.5 spike (S) #COVID19 booster? Find out by reading our preprint or this thread!

Led by @aletortorici

@HHMINEWS @UWBiochemistry

1/18

biorxiv.org/content/10.110…
Immune imprinting - AKA original antigenic sin - describes how the first exposure to a virus shapes the immunological outcome of subsequent exposures to antigenically related strains.

2/18
Last year, we showed that Omicron infection of Wuhan-Hu-1 (Wu) mRNA vaccinees recalls cross-reactive memory B cells specific for epitopes shared by multiple #SARSCoV2 variants rather than priming naive B cells binding Omicron RBD-specific epitopes

3/18
science.org/doi/10.1126/sc…
Image
Read 18 tweets
The Veesler Lab Profile picture
Sep 14, 2023
How do bat-borne sarbecoviruses (i.e. SARS-CoV-1/2-like viruses) interact with host receptors and are we ready for a possible future pandemic?

Find out in this study led by @0327jimin & @Sam_K_Zepeda !

@HHMINEWS @UWBiochemistry

1/23

biorxiv.org/content/10.110…
Spillover of SARS-CoV-1 and #SARSCoV2 from Rinolophus bat origin led to the SARS epidemic and the #COVID19 pandemic. Reports of additional sarbecovirus spillovers & detection in Rhinolophus bats and other animals underscore their recurrent zoonotic threat to public health

2/23
Clade 3 sarbecoviruses have been identified in Rhinolophus bats in Europe and Africa and comprise uncharacterized ACE2-utilizing viruses, broadening the range of sarbecoviruses with spillover potential

3/22
Read 23 tweets

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