In-Vivo Toxicity Studies and In-Vitro Inactivation of SARS-CoV-2 by Povidone-iodine In-situ Gel Forming Formulations

  1. Bo Liang
  2. Xudong Yuan
  3. Gang Wei
  4. Wei Wang
  5. Ming Zhang
  6. Haizhou Peng
  7. Amin Javer
  8. Michelle Mendenhall
  9. Justin Julander
  10. Sammi Huang
  11. Hany Michail
  12. Yong Lu
  13. Qi Zhu
  14. John Baldwin

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Abstract

To curb the spread of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, we characterize the virucidal activity of long-acting Povidone Iodine (PVP-I) compositions developed using an in-situ gel forming technology. The PVP-I gel forming nasal spray (IVIEW-1503) and PVP-I gel forming ophthalmic eye drop (IVIEW-1201) rapidly inactivated SARS-CoV-2, inhibiting the viral infection of VERO76 cells. No toxicity was observed for the PVP-I formulations. Significant inactivation was noted with preincubation of the virus with these PVP-I formulations at the lowest concentrations tested. It has been demonstrated that both PVP-I formulations can inactivate SARS-CoV-2 virus efficiently in both a dose-dependent and a time-dependent manner. These results suggest IVIEW-1503 and IVIEW-1201 could be potential agents to reduce or prevent the transmission of the virus through the nasal cavity and the eye, respectively. Further studies are needed to clinically evaluate these formulations in early-stage COVID-19 patients.

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    SciScore for 10.1101/2020.05.18.103184: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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: We detected the following sentences addressing limitations in the study:
    One of the major limitations of the drugs mentioned above is that there is no data available on the adverse reactions of the high dosages of the antiviral drugs when given for long durations. The duration of medication needed is also currently unknown (48). Studies have shown that the SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) in the lungs as a receptor and relies on an enzyme known as transmembrane protease serine 2 (TMPRSS2) to enter and fuse with host cells in order to replicate (49). This has led medical professionals to test existing antivirals that are known to interfere with viral membrane fusion and disrupt RNA polymerase in order to prevent further viral production in hosts. Hydroxychloroquine, an antimalarial and derivative of chloroquine, is one such therapy that is believed to be one of the potential therapies in treating COVID-19. Its mechanism has been used to prevent the transport of virions to the replication site by altering pH and block viral endocytosis to hosts (49). However, in a recent COVID-19 trial consisting of 36 patients, 14 patients treated with hydroxychloroquine have continued to show symptoms of upper or lower respiratory tract infections (50). Although hydroxychloroquine has increased potency and tolerable safety profile compared to chloroquine, potential adverse effects such as electrolyte imbalance and fatal dysrhythmias could take place (50). Another possible therapy, Remdesivir®, a nucleotide analogue, inhibits viral RNA p...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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

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  2. Version published to 10.1101/2020.05.18.103184v1 on bioRxiv