High-resolution profiling of pathways of escape for SARS-CoV-2 spike-binding antibodies

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  1. SciScore for 10.1101/2020.11.16.385278: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.


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    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are several important caveats to the results we obtained with Phage-DMS libraries. In general, phage libraries display linear peptides and therefore miss antibodies that bind to complex conformational epitopes, or at best provide a partial view of a linear portion of such epitopes. Additionally, the peptide libraries are amplified in bacteria and therefore lack glycans or other post-translational modifications. While these Phage-DMS-derived escape maps define mutations that could lead to loss of antibody binding, it is unknown whether the virus would tolerate mutations at those sites. In fact, a study examining the effect of mutations within the SARS-CoV-2 RBD demonstrated that many led to poor protein expression or loss of function (Starr et al., 2020). Thus, for the antibody targeting regions described here, which are in more conserved functional domains, the escape mutations should be further examined in the context of their mutational tolerance. These studies have defined common and variable escape mutations across 18 COVID-19 patients that will be useful for viral surveillance, particularly as SARS-CoV-2 S protein-based vaccines are introduced into the population. In addition, the Spike Phage-DMS library developed here could be useful for examining larger cohorts, potentially including those with variable clinical outcomes and individuals of variable ages, to define whether mutations that disrupt antibody binding vary in a systematic way across populations and whet...

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    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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