Key substitutions in the spike protein of SARS-CoV-2 variants can predict resistance to monoclonal antibodies, but other substitutions can modify the effects

SciScore for 10.1101/2021.07.16.452748: (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

Experimental Models: Cell Lines
Sentences	Resources
293T-ACE2/TMPRSS2 cells stably expressing ACE2 and transmembrane serine protease 2 (TMPRSS2) were established and maintained as previously described (51).	293T-ACE2/TMPRSS2 suggested: None
Recombinant DNA
Sentences	Resources
Plasmids and cell lines: Codon-optimized full-length S genes of SARS-COV-2 variants (using D614G as the base plasmid) were cloned into pCDNA3.1(+) (GenScript, Piscataway, NJ).	pCDNA3.1 suggested: RRID:Addgene_79663)
The HIV gag/pol (pCMVΔR8.2) and Luciferase reporter (pHR’CMV-Luc) plasmids were obtained from the Vaccine Research Center (National Institutes of Health, Bethesda, MD).	pCMVΔR8.2 suggested: None pHR’CMV-Luc suggested: None
Software and Algorithms
Sentences	Resources
Titers were calculated using a nonlinear regression curve fit (GraphPad Prism software Inc., La Jolla, CA).	GraphPad Prism suggested: (GraphPad Prism, RRID:SCR_002798)
Computational analysis: The amino acid locations on the RBD that affected nAb potency were modeled with PyMOL molecular graphics system (version 1.7.4; Schrödinger, LLC) using the Protein Data Bank (PDB) entries 6ZOZ for the closed conformation and 7A98 for the open conformation.	PyMOL suggested: (PyMOL, RRID:SCR_000305)

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Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

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Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

Finally, the safety and simplicity of pseudovirus neutralization assays offer many advantages for identifying MOCs and screening antibody therapeutics and vaccinee sera, but such assays have limitations. Pseudoviruses do not completely mimic authentic SARS-CoV-2 or virus entry conditions in vivo. In our nAb screens, we found that two antibodies that bind outside of the receptor binding motif could only partially neutralize (< 80%) pseudoviruses bearing WT Spike (data not shown). This inability to achieve complete neutralization by some nAbs has been observed by others using authentic SARS-CoV-2 (54, 68) and may be due to use of engineered target cells that permit efficient virus entry or heterogeneous glycosylation of Spike that affects an antibody epitope. Neutralization assays also cannot measure the potential protective activity afforded by nAb Fc effector functions. To address the limitations of any single assay, several consortia have formed to integrate findings from animal models and in vitro assays involving a variety of formats to inform the development of potent antibody therapeutics and other medical countermeasure that will remain potent against emerging variants.

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Results from TrialIdentifier: No clinical trial numbers were referenced.

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Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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Results from JetFighter: We did not find any issues relating to colormaps.

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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.
• No funding statement was detected.
• No protocol registration statement was detected.

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Results from scite Reference Check: We found no unreliable references.

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