Postinfection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Protease inhibitors targeting viral 3C-like protease are attractive therapeutic options for COVID-19. Here, we synthesized deuterated variants of a coronavirus protease inhibitor, GC376, and determined the therapeutic efficacy in a lethal mouse model. The transgenic mice infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of COVID-19, develop lung pathology resembling that of severe COVID-19 patients and were used for antiviral drug testing. The deuterated variants of GC376 have improved potency against SARS-CoV-2 in in vitro assays. Furthermore, treatment with a deuterated variant starting at 24 h postinfection resulted in significantly increased survival of mice compared to vehicle-treated mice. The results suggest that deuterated variants have excellent potential as antiviral agents against SARS-CoV-2.
Article activity feed
-
-
SciScore for 10.1101/2021.02.05.429937: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All experiments were conducted under protocols approved by the Institutional Biosafety Committee at the University of Iowa according to guidelines set by the Biosafety in Microbiological and Biomedical Laboratories, the U.S. Department of Health and Human Services, the U.S. Public Health Service, the U.S. Centers for Disease Control and Prevention, and the National Institutes of Health. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Post-infection treatment in a mouse model of SARS-CoV-2 infection: Compound 2 was examined for efficacy using 7-8 week-old female K18-hACE2 mice infected with SARS-CoV-2(26). SciScore for 10.1101/2021.02.05.429937: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All experiments were conducted under protocols approved by the Institutional Biosafety Committee at the University of Iowa according to guidelines set by the Biosafety in Microbiological and Biomedical Laboratories, the U.S. Department of Health and Human Services, the U.S. Public Health Service, the U.S. Centers for Disease Control and Prevention, and the National Institutes of Health. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Post-infection treatment in a mouse model of SARS-CoV-2 infection: Compound 2 was examined for efficacy using 7-8 week-old female K18-hACE2 mice infected with SARS-CoV-2(26). Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Briefly, confluent Vero E6 cells were inoculated with SARS-CoV-2 at 50-100 plaque forming units/well, and medium containing various concentrations of each compound and agar was applied to the cells. Vero E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Post-infection treatment in a mouse model of SARS-CoV-2 infection: Compound 2 was examined for efficacy using 7-8 week-old female K18-hACE2 mice infected with SARS-CoV-2(26). K18-hACE2suggested: RRID:IMSR_GPT:T037657)Software and Algorithms Sentences Resources The 50% effective concentration (EC50) values were determined by GraphPad Prism software using a variable slope (GraphPad, La Jolla, CA)(17). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Statistical analysis: Multiple T-test were used to analyze body weight change and lung virus titers between groups using GraphPad Prism Software version 6 (San Diego, CA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your data.
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.
-
