The peer-reviewed version of our manuscript describing the broadly neutralizing sarbecovirus antibody S2K146 can be found here…

Here is the original thread describing these results.

Compared to our original @biorxivpreprint submission, we added data showing that S2K146 binds the reconstructed RBD ancestor of all sarbecoviruses (AncAsia)

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And that S2K146 affinity maturation allows it to be more resilient to mutations (including all individual mutations found in #OmicronVariant) than the unmutated germline precursor

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Finally, we showed in this recent paper that S2K146 potently neutralizes the #OmicronVariant !

Thanks @Nature for highlighting our work!…

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More from @veeslerlab

31 Dec 21
We characterized the structural basis of #SARSCoV2 #OmicronVariant binding to the host ACE2 receptor and neutralization by the S309/sotrovimab clinical antibody therapeutic!

Led by @Dr_MattMcCallum & Nadine Czudnochowski Collab w Gyorgy Snell

We show that the #OmicronVariant spike NTD antigenic supersite is structurally rearranged, relative to the Wuhan-Hu-1 NTD, explaining the loss of binding and neutralization by a panel of NTD-targeted monoclonal antibodies we recently evaluated (…).

The #OmicronVariant spike S2 subunit (fusion machinery) harbors mutations introducing additional electrostatic contacts with the S1 subunit, which might explain the reduced S1 shedding described in this preprint (…)

Read 8 tweets
21 Dec 21
Can we correlate #SARSCoV2 spike (S) biochemical properties with the specificity, magnitude & quality of antibody responses? Put another way, how to make a good #CovidVaccine ?

@johnbowenbio led the charge to answer these questions


We compared antibody responses elicited by 6 #CovidVaccine distributed globally: Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, AstraZeneca AZD1222, Gamaleya Sputnik V and Sinopharm BBIBP-CorV, after 2 doses, Janssen Ad26.COV2.S after 1 dose, and human convalescent plasma

Prefusion S/S2, RBD & NTD antibody binding titers were highest after 2 doses of mRNA-1273 or BNT162b2 and lowest for 1 dose of Ad26.COV2.S. The other 2 dose vaccines and #SARSCoV2 infection resulted in intermediate binding titers.

Read 22 tweets
14 Dec 21
Here is our assessment of #SARSCoV2 #Omicron receptor usage and immune evasion in collaboration with the team of @DavideCorti6 @Vir_Biotech

Led by Elisabetta Cameroni, Christian Saliba, @johnbowenbio & Laura E. Rosen

@HHMINEWS @UWBiochemistry…

#SARSCoV2 #Omicron harbors a staggering 37 amino acid mutations in the spike with 15 of them in the receptor-binding domain (RBD), which is the main target of neutralizing antibodies. The number and positions of these mutations is concerning for tropism & immune evasion.

We found that the #SARSCoV2 #Omicron RBD has ~2.5-fold enhanced ACE2 binding affinity, relative to the Wuhan-Hu-1 RBD, similar to what we previously showed for the Beta variant of concern.…

Read 8 tweets
10 Dec 21
Are you wondering what antibody responses are like in #SARSCoV2 Delta breakthrough patients?

We answer this question and many others in this study led by @coronalexington

@HHMINEWS @UWBiochemistry…

We followed 4 cohorts longitudinally for up to 6 months:
-Delta breakthrough (vaccinated then infected)
-subjects infected and then vaccinated (2x and 3x)
-vaccinated-only (2x and 3x)

in collaboration with @HelenChuMD and her HAARVI team.

Serum IgG binding titers correlated with the number of SARS-CoV-2 spike 'exposures' through vaccination and/or infection and were therefore highest for 3x vaccinated subjects (infected or not) and Delta breakthrough cases.

Read 15 tweets
26 Oct 21
Have you heard of the recently discovered 8th human-infecting #coronavirus designated CCoV-HuPn-2018?
We reveal the architecture of its spike (ie infection machinery), receptor usage and antigenic properties!

Led by @aletortorici

CCoV-HuPn-2018 is a canine-feline recombinant alpha-#coronavirus isolated from the respiratory swab of a child hospitalized with pneumonia, indicating that more coronaviruses are spilling over to humans than previously appreciated.

We determined #cryoEM structures of the CCoV-HuPn-2018 spike in two markedly different conformational states which we propose to correspond to two snapshots of viral entry.

Read 12 tweets
14 Oct 21
We identified a broadly neutralizing sarbecovirus antibody (S2K146) in collaboration with Matteo Samuele Pizzuto & @DavideCorti6
Work led by @YoungjunPark11 Anna De Marco @tylernstarr @JZhuoming

S2K146 binds and broadly neutralizes several SARS-CoV-1-like and SARS-CoV-2-like viruses (clades 1a/1b). It inhibits BtKY72 (clade 3) K493Y/T498W S pseudovirus, as we previously showed that these 2 mutations enable this bat virus to use hACE2.…

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Our #cryoEM structure reveals that S2K146 'mimics' ACE2, as 75% of the residues participating in the epitope are also part of the ACE2 binding site, and is therefore not affected by known variants.

3/7 Image
Read 7 tweets

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