The Effect of Minnelide against SARS-CoV-2 in a Murine Model
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of coronavirus disease 2019, COVID-19, and the current COVID-19 pandemic. Even as more vaccine candidates are released, more treatment options are critically needed. Here, we investigated the use of Minnelide, a water soluble pro-drug with anti-inflammatory properties, for the treatment of COVID-19. To do this, k18-hACE2 mice were infected with SARS-CoV-2 or given PBS control intranasally. The next day mice were either treated daily with low dose (0.0025mg/day) or high dose Minnelide (0.005mg/day), or given vehicle control intraperitoneal. Mice were weighed daily, and sacrificed at day 6 and 10 post-infection to analyze viral burden, cytokine response, and pathology. We observed a reduction in viral load in the lungs of Minnelide-treated mice infected with SARS-CoV-2 at day 10 post-infection compared to day 6 post-infection. All SARS-CoV-2 infected non-treated mice were moribund six days post-infection while treatment with Minnelide extended survival for both low (60% survival) and high (100% survival) dose treated mice ten days post-infection. Interestingly, cytokine analysis demonstrated a significant reduction in IL-6 (lung and heart) and D-dimer (serum) in high dose treated SARS-CoV-2 infected mice compared to mice infected with SARS-CoV-2 alone at day 6 post-infection. Additionally, histology analysis revealed that Minnelide treatment significantly improved lung pathology ten days post-infection with SARS-CoV-2 with all the mice exhibiting normal lung tissue with thin alveolar septa and no inflammatory cells. Overall, our study exhibits potential for the use of Minnelide to improve survival in COVID-19 patients.
Article activity feed
-
SciScore for 10.1101/2021.05.05.442875: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All procedures were approved by the Institutional Animal Care and Use Committee (protocol number 20-005) of Northern Arizona University. 4.2 Virus and Media: This study used coronavirus SARS-CoV-2 isolate USA-WA1/2020 (NR-52281; BEI Resources, Manassas, VA, USA). Sex as a biological variable hACE2 male and female mice (6-8 weeks) were used for these studies according to NIH guidelines for housing and care in a biosafety level 3 animal laboratory. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Briefly, a t175 flask that was ~50% confluent was infected with … SciScore for 10.1101/2021.05.05.442875: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All procedures were approved by the Institutional Animal Care and Use Committee (protocol number 20-005) of Northern Arizona University. 4.2 Virus and Media: This study used coronavirus SARS-CoV-2 isolate USA-WA1/2020 (NR-52281; BEI Resources, Manassas, VA, USA). Sex as a biological variable hACE2 male and female mice (6-8 weeks) were used for these studies according to NIH guidelines for housing and care in a biosafety level 3 animal laboratory. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Briefly, a t175 flask that was ~50% confluent was infected with SARS-CoV-2 virus, whereby 10 mL of fresh 2% FBS growth media containing 100μL of the BEI viral stock was added to VeroE6 cells and gentle rocked on a rocking platform for 1 h at room temperature. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Experimental Models: Organisms/Strains Sentences Resources 4.1 Mice: The K18-hACE2 COVID-19 transgenic mouse model (B6.Cg-Tg (K18-ACE2)2Primm/J, Stock No. 034860, Jackson Laboratory, Bar Harbor, ME, USA) was used in the current study. B6.Cg-Tg (K18-ACE2)2Primm/Jsuggested: NoneSoftware and Algorithms Sentences Resources Sections were then processed for H&E staining and submitted to pathologist for analysis. 4.7 Statistical Analysis: Differences in data were tested for significance using either GraphPad Prism for Windows (GraphPad, USA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)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 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:- No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
- 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.
Results from scite Reference Check: We found no unreliable references.
-
