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Authors: Wrapp et al.

Link to paper: https://www.cell.com/pb-assets/products/coronavirus/CELL_CELL-D-20-00891.pdf

Journal/ Pre-Print: Cell

Tags: Immunology/Immunity, Modelling, Structural biology, Cell biology, Therapeutics, Vaccines, Virology

Research Highlights 

1. Isolation of single domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes and crystal structures of the interactions give epitope maps

2. VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses and cross reactivity against SARS-CoV-2 S

3. VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc fusion

Summary 

The isolation of single domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes found VHHs that neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses. Structural studies reveal two distinct epitopes on the spike protein of MERS-CoV and SARS-CoV-1, but both VHHs interfere with receptor binding. Cross-reactivity of these VHHs was demonstrated (SARS-CoV-1 S-directed VHH and SARS-CoV-2 S) and they show that this cross reactive VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc fusion. These are suggested to be potential therapeutics that could be administered by nebulizing spray.

Impact for SARS-CoV2/COVID19 research efforts

Understand the virology and/or cell biology of SARS-CoV2/COVID19

Develop a vaccine for SARS-CoV2/COVID19

Inhibit of SARS-CoV2/COVID19 transmission

Treat of SARS-CoV2/COVID19 positive individuals

Study Type

· In silico study / bioinformatics study

· In vitro study

Strengths and limitations of the paper

Novelty: New epitopes and VHHs produced and good structural data complemented with SPR and neutralisation assays to characterise them.

Standing in the field: Novel approach and maps other known antibodies on to the MERS-CoV or SARS-CoV-1 spike proteins.

Appropriate statistics: Yes

Viral model used: SARS-CoV-2 S VSV psuedoparticles

Translatability: Basis for design of VHHs and nebulizing spray due to stability of theses VHHs.

Main limitations: The approach was clearly started a number of years ago and was targeting MERS-CoV or SARS-CoV-1. The VHHs are therefore maybe not optimal for SARS-CoV-2 but do show cross reactivity. However this study would benefit from data demonstrating activity against genuine SARS-CoV-2 virus instead against a pseudovirus particle.