A comparison of Remdesivir versus Au 22 Glutathione 18 in COVID-19 golden hamsters: a better therapeutic outcome of gold compound

  1. Zhesheng He
  2. Fei Ye
  3. Chunyu Zhang
  4. Jiadong Fan
  5. Zhongying Du
  6. Wencong Zhao
  7. Qing Yuan
  8. Wenchao Niu
  9. Fuping Gao
  10. Bo He
  11. Peng Cao
  12. Lina Zhao
  13. Xuejiao Gao
  14. Xingfa Gao
  15. Bo Sun
  16. Yuhui Dong
  17. Jincun Zhao
  18. Jianxun Qi
  19. Huaidong Jiang
  20. Yong Gong
  21. Wenjie Tan
  22. Xueyun Gao

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Abstract

We firstly disclose single compound yields better therapeutic outcome than Remdesivir in COVID-19 hamster treatments as it is armed with direct inhibition viral replication and intrinsic suppression inflammatory cytokines expression. Crystal data reveals that Au (I), released from Au 22 Glutathione 18 (GA), covalently binds thiolate of Cys145 of SARS-CoV-2 M pro . GA directly decreases SARS-CoV-2 viral replication (EC50: ~0.24 μM) and intrinsically down-regulates NFκB pathway therefore significantly inhibiting expression of inflammatory cytokines in cells. The lung viral load and inflammatory cytokines in GA-treated COVID-19 transgenic mice are found to be significantly lower than that of control mice. When COVID-19 golden hamsters are treated by GA, the lung inflammatory cytokines levels are significantly lower than that of Remdesivir while their lung viral load are decreased to same level. The pathological results show that GA treatment significantly reduce lung inflammatory injuries when compared to that of Remdesivir-treated COVID-19 golden hamsters.

One Sentence Summary

We found that gold cluster molecule directly inhibits SARS-CoV-2 replication and intrinsically suppresses inflammatory cytokines expression in COVID-19 transgenic mouse and golden hamster model, gold cluster providing a better lung injury protection than Remdesivir in COVID-19 golden hamsters via intranasally dropping administration.

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  1. Version published to 10.1101/2020.10.16.342097v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.10.16.342097: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The studies of mice LD50: 100 adult female BALB/c mice for experiments were conducted in compliance with regulations of the National Act on the use of experimental animals (China) and were approved by the Institutional animal care and ethic committee at the Chinese Academy of Sciences (approved No. SYXK (jing) 2014-0023).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe studies of mice LD50: 100 adult female BALB/c mice for experiments were conducted in compliance with regulations of the National Act on the use of experimental animals (China) and were approved by the Institutional animal care and ethic committee at the Chinese Academy of Sciences (approved No. SYXK (jing) 2014-0023).
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After blocking, the membrane was incubated with specific antibodies for COX‐ 2 (Cell Signaling Technologies, 12282, 1:1000), IL‐1β (Cell Signaling Technologies, 12703, 1:1000), IL ‐ 6 (Cell Signaling Technologies, 12912, 1:1000), TNF ‐ α (Cell Signaling Technologies, 11948, 1:1000), phosphor‐p65 (Cell Signaling Technologies, 3033
    IL ‐ 6 (Cell Signaling Technologies, 12912
    suggested: None
    TNF ‐ α (Cell Signaling Technologies, 11948
    suggested: None
    phosphor‐p65
    suggested: None
    , 1:1000), p65 (Cell Signaling Technologies, 3034, 1:1000), phosphor‐ IκBα (Cell Signaling Technologies, 2859, 1:1000), IκBα (Cell Signaling Technologies, 4812, 1:1000), IKKα (Cell Signaling Technologies, 2682, 1:1000), IKKβ (Cell Signaling Technologies, 8943, 1:1000), phosphor‐ IKKα/β (Cell Signaling Technologies, 2697, 1:1000), followed by incubation with an appropriate secondary antibody conjugated to horseradish peroxidase (Beyotime Biotechnology, China)
    p65
    suggested: (Cell Signaling Technology Cat# 3034, RRID:AB_330561)
    Experimental Models: Cell Lines
    SentencesResources
    Vero cells were infected with SARS-CoV-2 at a multiplicity of infection (MOI) of 0.015 diluted in DMEM/F12 without FCS at 37°C for 1 h.
    Vero
    suggested: None
    Western blot analysis of NFκB and inflammatory cytokine in macrophage and bronchial epithelial cell: RAW 264.7 or 16HBE cell were seeded into 6 well plates at a density of 2 × 106cells/well.
    RAW 264.7
    suggested: None
    Cell toxicity of gold compounds in Vero E6, RAW264.7 and 16HBE cell line: Serial dose of auranofin or gold cluster were added into cell culture media, respectively.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Experimental Models: Organisms/Strains
    SentencesResources
    The studies of mice LD50: 100 adult female BALB/c mice for experiments were conducted in compliance with regulations of the National Act on the use of experimental animals (China) and were approved by the Institutional animal care and ethic committee at the Chinese Academy of Sciences (approved No. SYXK (jing) 2014-0023).
    BALB/c
    suggested: None

    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.

  3. Version published to 10.1101/2020.10.16.342097v1 on bioRxiv