Thread by @veeslerlab

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

biorxiv.org/content/10.110…

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#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.

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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.

nature.com/articles/s4158…

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We discovered that the #SARSCoV2 #Omicron RBD, but not Alpha or Beta RBDs, bound mouse ACE2, likely due to Q493R which is similar to Q493K isolated upon mouse adaptation by @Baric_Lab

sciencedirect.com/science/articl…

These data *putatively* reflect #Omicron expanded tropism

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#SARSCoV2 #Omicron immune evasion reduces plasma neutralizing activity up to 57x (convalescent) and up to 30-40x for Pfizer, Moderna or Astrazeneca vaccinees.
No neutralizing activity left with J&J (1x), Sputnik and Sinopharm for most subjects analyzed.

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#SARSCoV2 #Omicron mutations knock out 7 out of 8 monoclonal antibodies currently used in the clinic. Only S309, the parent of VIR-7832, retain neutralizing activity, with ~3x reduction relative to Wuhan-Hu-1.

We described S309 early last year.
nature.com/articles/s4158…

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A few other broadly neutralizing sarbecovirus antibodies are inhibiting #SARSCoV2 #Omicron, including S2X259, S2H97 and S2K146. This is good news and shows that targeting conserved sarbecovirus RBD epitopes provides resilience to viral evolution!

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Thank you so much @SamK_Zepeda Kaiti Sprouse @coronalexington and all our wonderful collaborators including @atelentia @LanzavecchiaB @HelenChuMD @LucaPiccoli9 @SkiClimbSciNick @DrLisaPurcell and many others not on twitter!

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