Ivermectin reduces in vivo coronavirus infection in a mouse experimental model
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Abstract
The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.
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SciScore for 10.1101/2020.11.02.363242: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Experimental protocols were opportunely approved by the Institutional Animal Care and Use Committee (protocol #008-16) and were performed according to national law #18.611 and international guidelines. Randomization Female mice were randomly distributed in three experimental groups: Infected Blinding At necropsy, liver appearance was blindly scored (0 to 3) by an independent trained technician considering the main pathologic pattern of MHV infection (Macphee et al., 1985; Perlman, 1998). Power Analysis not detected. Sex as a biological variable Animals and management: A total of 56 BALB/cJ female mice (6-8 weeks old) were bred at the Transgenic and Experimental … SciScore for 10.1101/2020.11.02.363242: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Experimental protocols were opportunely approved by the Institutional Animal Care and Use Committee (protocol #008-16) and were performed according to national law #18.611 and international guidelines. Randomization Female mice were randomly distributed in three experimental groups: Infected Blinding At necropsy, liver appearance was blindly scored (0 to 3) by an independent trained technician considering the main pathologic pattern of MHV infection (Macphee et al., 1985; Perlman, 1998). Power Analysis not detected. Sex as a biological variable Animals and management: A total of 56 BALB/cJ female mice (6-8 weeks old) were bred at the Transgenic and Experimental Animal Unit of Institut Pasteur de Montevideo, under specific pathogen free conditions in individually ventilated racks (IVC, 1285L, Tecniplast, Milan, Italy). Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The following fluorophore-conjugated antibodies were used: Anti-CD4-FITC (#11004181, clone GK1.5) and anti-CD8-PE-Cy7 (#25008182, clone 53-6.7) from eBioscience™ (San Diego, CA, USA) and anti-CD19-PerCP-Cy™ 5.5 (#551001, clone ID3), from BD Pharmingen (San Diego, CA, USA) Anti-CD4-FITC ( #11004181suggested: Noneanti-CD8-PE-Cy7suggested: Noneanti-CD19-PerCP-Cy™suggested: NoneExperimental Models: Cell Lines Sentences Resources MHV-A59 preparation: MHV-A59 (ATCC® VR-764™) viruses were expanded in murine L929 cells (ATCC® CCL-1™) to reach a concentration of 1×107 plaque forming unit (PFU)/mL. L929suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Animals and management: A total of 56 BALB/cJ female mice (6-8 weeks old) were bred at the Transgenic and Experimental Animal Unit of Institut Pasteur de Montevideo, under specific pathogen free conditions in individually ventilated racks (IVC, 1285L, Tecniplast, Milan, Italy). BALB/cJsuggested: NoneSoftware and Algorithms Sentences Resources , InfoStat software (Di Rienzo et al., 2017), which included the treatments (three groups) and time (pre and postinfection) as fixed variables and the animals and replicates as random variables. InfoStatsuggested: (InfoStat, RRID:SCR_014310)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:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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