Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies
immunology/immunity structural biology therapeutics virology
Authors: Wrapp et al.
Journal/ Pre-Print: Cell
Tags: Immunology/Immunity, Modelling, Structural biology, Cell biology, Therapeutics, Vaccines, Virology
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
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
· 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.