SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface

Authors: Bertoglio et al.

Link to paper: https://doi.org/10.1101/2020.06.05.135921

Journal/ Pre-Print: BioRxiv

Tags: Molecular Biology, Structural Biology, Therapeutics

Research Highlights 

1. Describes a number of antibodies which may be therapeutically useful against SARS-Cov2

2. Describes synergy between antibodies

3. The antibodies described in this study were produced using phage display, rather than from recovered volunteers

Summary

Phage display was used to produce an array of antibodies with strong binding to the RBD, S1 and S1-S2 of SARS-CoV-2. Some antibodies inhibited the interaction between these proteins and ACE2 receptors on Calu-3 and Expi293F cell lines. Combinations of antibodies showed synergy. These antibodies also neutralized SARS-CoV-2 in a VeroE6 cell line. Epitope mapping to the RBD was carried out for some antibodies to determine their binding site. In silico simulations followed to produce 3D atomic structure of the antibody-RBD interactions. This showed five antibodies binding at the RBD-ACE2 interface and two antibodies inhibiting ACE2 binding allosterically.

Impact for SARS-CoV2/COVID19 research efforts

Treament of SARS-CoV2/COVID19 positive individuals

Study Type

· In silico study / bioinformatics study

· In vitro study

Strengths and limitations of the paper

Novelty: Lists some possible antibodies which could be used to treat Covid-19 patients

Standing in the field: Builds on other similar work, also some questionable citations

Appropriate statistics: Lack of information regarding statistics

Viral model used: SARS-CoV-2/Münster/FI110320/1/2020

Translatability: Requires further information and experiments to be translatable

Main limitations:

· Lacks clarity in figures and results, as well as writing - difficult to decipher what the authors are trying to show us

· Did not use the Calu-3 lung cells in the neutralization assay

· 10 out of the 17 potential antibodies have inexplicably not been used further in the results

· Less than 1:1 ratio of antibody to antigen binding for EC50 compared with similar results in a Botulinum toxin study with no explanation for the comparison

· Useful to have had a quantitative comparison of synergy for the antibody combinations

· Would have been useful to combine more than two antibodies for synergy