Thread by @FISchmidtLab

As a team of scientists from @scrippsresearch @karolinskainst @UniBonn @UniklinikBonn @IIIBonn @uni_tue @Illinois_Alma, we identified four potent neutralizing camelid nanobodies ...

https://twitter.com/FISchmidtLab/status/1349036946706886657

Solved the #Xray structure of all four #nanobodies in complex with #SARSCoV2 spike #RBD @wchnihcholas and Ian Wilson ...

Used #CryoEM to determine that VHH E stabilizes the 3-up conformation of trimeric #SARSCoV2 spike @BMartinHallberg ...

Engineered bivalent and trivalent constructs of synergistic #nanobodies based on the structural information. This improved #neutralization activity by a factor of up to 100 ...

Constructed chimeric viruses to perform #evolution experiment coupled to #NGS to determine rapid emergence of #escape mutants to monomeric nanobodies. Bivalent VHHs targeting two epitopes of spike prevented emergence of resistant mutants.
@k_u_ludwig @schmidburgk ...

Used #spike expressing cells (green or red) to show that some #VHHs activate the fusion machinery of #SARSCoV2 #spike (note mixture of green and red cellular content), likely by mimicking ACE2 binding (inducing the 3-up conformation of spike).

We propose that #nanobody binding triggers the premature formation of the #postfusion conformation, thus destroying #spike on #virions before they get the chance to infect cells ..

Kudos to @Geyer_lab for #SPR measurements, the Schindler and Kümmerer labs for #BSL3 work, and every author for days and nights in the lab and in front of the computer, including @cfnanobodies @FlorianNGohr @YM_Tesfamariam @schmidburgk @k_u_ludwig @wchnicholas @BMartinHallberg

Thanks to all the authors jointly led by Paul-Albert König @cfnanobodies, @wchnicholas, @BMartinHallberg, and @FISchmidtLab, including @Geyer_lab (SPR), Beate Kümmerer and Michael Schindler labs for #BSL3 work, @FlorianNGohr @YM_Tesfamariam @schmidburgk @k_u_ludwig

@wchnicholas