Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host Lectins and Lung Microbiota

Authors: Fabrizio Chiodo, Sven C.M. Bruijns, Ernesto Rodriguez, R.J. Eveline Li, Antonio Molinaro, Alba Silipo, Flaviana Di Lorenzo, Dagmar Garcia-Rivera, Yury Valdes-Balbin, Vicente VerezBencomo and Yvette van Kooyk

Link to paper: https://doi.org/10.1101/2020.05.13.092478

Journal/ Pre-Print: bioRxiv

Tags: Immunology/Immunity, Cell Biology, Molecular Biology

Research Highlights 

1. Recombinant SARS-CoV2 spike protein can interact with human C-type lectins and sialic-acid binding lectins

2. SARS-CoV2 spike protein can interact with bacterial glycoconjugates

Summary

This paper is a preliminary study investigating SARS-CoV2 spike protein interactions to host glycoproteins. The authors design a range of immunoassays to test spike protein interactions. The first few experiments use wells coated with recombinant SARS-CoV-2 spike protein (figure 1-2) followed by ELISAs coated with bacterial glycoconjugates (figures 3-4). This study is missing a clear narrative and well-designed quantitative experiments. The assays don’t appear to be validated or robust. Further experimentation is needed before any inferences can be made from these results. 

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

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

Study Type

· In vitro study

Strengths and limitations of the paper

Novelty: Looking at ACE2 independent interactions with the SARS-CoV2 spike protein

Standing in the field: The concept is interesting, but the study did not adequately investigate the hypothesis

Appropriate statistics: No statistics were performed

Viral model used: coated ELISAs with recombinant SARS-CoV2 spike protein from human cell line

Translatability: no

Main limitations:

· This paper is lacking statistics, the authors only provide a qualitative analysis of their results.

· The n number is at the minimal of 3 in each experiment and there is no mention of any statistics done to compare duplicates.

· No cell biology to determine the relevance in disease.

· The ELISA assays are not quantitative, nor have the authors mentioned whether any validation work was performed on these assays that they have created. They have only briefly and inadequately commented on this in the supplementary materials: “The high positive binding of the viral spike protein to the different lectins in our experiments, was comparable to all the positive controls used. We are aware that ELISA are not quantitative experiments especially comparing different macromolecules (spike protein, Mannan etc), but having the positive results in the same OD range, provides a solid interpretation of our data.”

· Assays lack appropriate positive and negative controls