A SCID Mouse Model To Evaluate the Efficacy of Antivirals against SARS-CoV-2 Infection
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Abstract
Unlike the ancestral SARS-CoV-2 strain, the Beta (B.1.351) variant of concern has been reported to replicate to some extent in WT mice (C57BL/6 and BALB/c). We demonstrate here that infection of SCID mice with the Beta variant resulted in high viral loads in the lungs on day 3 postinfection.
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SciScore for 10.1101/2022.05.13.491916: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Euthanasia Agents: At different time-points post-infection (pi), 10 animals were euthanized by intraperitoneal (IP) injection of 100 μL Dolethal (200 mg/mL sodium pentobarbital, Vétoquinol SA) for collection of lung tissues.
IRB: Ethics: Housing conditions and experimental procedures were approved by the ethics committee of animal experimentation of KU Leuven (license P001/2021).Sex as a biological variable SARS-CoV-2 infection of SCID mice: In brief, 7-9 weeks old male severe combined immune deficient (SCID) mice were purchased from Janvier Laboratories. Randomization not detected. Blinding Tissue sections (5 μm) were analyzed after staining with hematoxylin and eosin and scored blindly for lung … SciScore for 10.1101/2022.05.13.491916: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Euthanasia Agents: At different time-points post-infection (pi), 10 animals were euthanized by intraperitoneal (IP) injection of 100 μL Dolethal (200 mg/mL sodium pentobarbital, Vétoquinol SA) for collection of lung tissues.
IRB: Ethics: Housing conditions and experimental procedures were approved by the ethics committee of animal experimentation of KU Leuven (license P001/2021).Sex as a biological variable SARS-CoV-2 infection of SCID mice: In brief, 7-9 weeks old male severe combined immune deficient (SCID) mice were purchased from Janvier Laboratories. Randomization not detected. Blinding Tissue sections (5 μm) were analyzed after staining with hematoxylin and eosin and scored blindly for lung damage by an expert pathologist. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources A passage two virus on Vero E6 cells was used for the study described here. Vero E6suggested: RRID:CVCL_XD71)Experimental Models: Organisms/Strains Sentences Resources Treatment Regimen: Male SCID mice were treated by oral gavage with either the vehicle (n=20) or Molnupiravir (EIDD-2801, n=14) at 200 mg/kg or Nirmatrelvir (PF-332, n=14) at 300 mg/kg, twice daily starting from D0, just before the infection with the Beta variant as described in the previous section. SCIDsuggested: NoneSoftware and Algorithms Sentences Resources Statistics: GraphPad Prism (GraphPad Software, Inc.) was used to perform statistical analysis. 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: We detected the following sentences addressing limitations in the study:On the other hand, the limitation of this model, is that unlike for hamsters, mice are only susceptible to the beta variant. Since small molecule inhibitors should have equipotent activity against all variants this is not of concern for studies with such drugs. However, for testing of therapeutic antibodies, infection models (in hamsters) with the different VoC will still be needed. Likewise, for vaccine studies, fully immunocompetent animals are needed, hence SCID mice are not useful for this purpose. Therefore, this SCID mice/beta variant infection model will be mainly advantageous for the evaluation of small molecule inhibitors of SARS-CoV-2 replication.
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:- 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.
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