Potent Neutralization of SARS-CoV-2 by Hetero-Bivalent Alpaca Nanobodies Targeting the Spike Receptor-Binding Domain

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Abstract

To date, SARS-CoV-2 has caused tremendous loss of human life and economic output worldwide. Although a few COVID-19 vaccines have been approved in several countries, the development of effective therapeutics, including SARS-CoV-2 targeting antibodies, remains critical.

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  1. SciScore for 10.1101/2021.02.02.429311: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Phage display library construction: The experiments involved alpacas were approved by a local ethics committee.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableTwo female alpacas were immunized by 2 times of subcutaneous injection and 1 time of intramuscular injection, each with 500 μg SARS-CoV-2 RBD in PBS, which was emulsified with an equal volume of Freund’s adjuvant (Sigma Aldrich).
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After incubation in RBD coated wells and standard washing, bound Nb-Fc was detected with a monoclonal anti-IgG1 Fc-HRP antibody.
    anti-IgG1 Fc-HRP
    suggested: (SouthernBiotech Cat# 9054-05, RRID:AB_2796627)
    After 2 days of infection, the cells were fixed with 4% paraformaldehyde, permeabilized with 0.1% Triton-100, blocked with DMEM containing 10% FBS, and stained with a rabbit monoclonal antibody against SARS-CoV-2 NP (GeneTex, GTX635679) and an Alexa Fluor 488-conjugated goat anti-mouse secondary antibody (ThermoFisher Scientific).
    SARS-CoV-2 NP
    suggested: None
    GTX635679
    suggested: (GeneTex Cat# GTX635679, RRID:AB_2888553)
    anti-mouse
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The expression vectors were transiently transfected to human HEK293F cells with polyethylenimine (Polyscience).
    HEK293F
    suggested: RRID:CVCL_6642)
    The antibody and virus mixture were then added to Vero E6 cells in 96-well plates (Corning).
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Each experiment was repeated twice, and the data were fitted with Prism to obtain the Tm values.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    The total number of cells, as indicated by the nuclei staining, and the infected cells, as indicated by the NP staining, were quantified with the cellular analysis module of the Gen5 software (BioTek).
    Gen5
    suggested: (Gen5, RRID:SCR_017317)

    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).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


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


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


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.