Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model
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Abstract
The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a M pro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice. Overall outcome of clinical symptoms and survival upon SARS-CoV-2 challenge were not improved in mice treated with GC-376 compared to controls. The treatment with GC-376 slightly improved survival from 0 to 20% in mice challenged with a high virus dose at 10 5 TCID50/mouse. Most notably, GC-376 treatment led to milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls in mice challenged with a low virus dose at 10 3 TCID50/mouse. This was particularly the case in the brain where a 5-log reduction in viral titers was observed in GC-376 treated mice compared to vehicle controls. This study supports the notion that GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection and that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2.
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SciScore for 10.1101/2021.01.27.428428: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Ethics Statement: Studies were approved by the Institutional Animal Care and Use Committee. Randomization Mice were randomly distributed in the number of groups (Fig 1A), anesthetized with isoflurane and challenged intranasally (i.n.) with 50 µl of either phosphate buffer saline (PBS), or 1×103 TCID50/mouse or 1×105 TCID50/mouse. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mouse studies: 6-week-old female K18-hACE2 mice were purchased from Jackson laboratories (Bar Harbor, ME). Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Viral stocks were prepared in Vero E6 Pasteur … SciScore for 10.1101/2021.01.27.428428: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Ethics Statement: Studies were approved by the Institutional Animal Care and Use Committee. Randomization Mice were randomly distributed in the number of groups (Fig 1A), anesthetized with isoflurane and challenged intranasally (i.n.) with 50 µl of either phosphate buffer saline (PBS), or 1×103 TCID50/mouse or 1×105 TCID50/mouse. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mouse studies: 6-week-old female K18-hACE2 mice were purchased from Jackson laboratories (Bar Harbor, ME). Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Viral stocks were prepared in Vero E6 Pasteur cells. Vero E6suggested: RRID:CVCL_XD71)Experimental Models: Organisms/Strains Sentences Resources Mouse studies: 6-week-old female K18-hACE2 mice were purchased from Jackson laboratories (Bar Harbor, ME). K18-hACE2suggested: RRID:IMSR_GPT:T037657)Software and Algorithms Sentences Resources Graphs/Statistical analyses: All data analyses and graphs were performed using GraphPad Prism software version 8 ( GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPad Software Inc. 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: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04426695 Recruiting Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-Co… 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.
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