Designed variants of ACE2-Fc that decouple anti-SARS-CoV-2 activities from unwanted cardiovascular effects
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SciScore for 10.1101/2020.08.13.248351: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: ACE2-Fc pharmacokinetics in mice: Institutional Animal Care and Use Committee of the Northwestern University approved the animal procedure in this study (approved protocol number IS00009990). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Briefly, a bolus intravenous injection of ACE2-Fc proteins (0.5mg/kg body weight) was performed in 10 weeks old female BALB/c mice. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources When cells reached 50-100% density in the wells, the culture media were tested for their ACE2-Fc contents using a custom ELISA (anti-ACE2 antibody [Abcam, … SciScore for 10.1101/2020.08.13.248351: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: ACE2-Fc pharmacokinetics in mice: Institutional Animal Care and Use Committee of the Northwestern University approved the animal procedure in this study (approved protocol number IS00009990). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Briefly, a bolus intravenous injection of ACE2-Fc proteins (0.5mg/kg body weight) was performed in 10 weeks old female BALB/c mice. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources When cells reached 50-100% density in the wells, the culture media were tested for their ACE2-Fc contents using a custom ELISA (anti-ACE2 antibody [Abcam, Cambridge, MA] for capturing and anti-human IgG-Fc-HRP [SouthernBiotech, Birmingham, AL] for detection). anti-ACE2suggested: (Abcam Cat# ab239924, RRID:AB_2861381)After overnight incubation at 4°C, the wells were washed three times with TBST buffer before HRP-conjugated anti-human IgG-Fc secondary antibody was added. anti-human IgG-Fcsuggested: NoneThe levels of ACE2-Fc in the sera were measured by ELISA using anti-ACE2 capturing antibody and anti-human IgG-Fc-HRP antibody for detection as described above. anti-human IgG-Fc-HRPsuggested: NoneExperimental Models: Cell Lines Sentences Resources Briefly, HEK293 cells were transfected with individual ACE2-Fc variants by standard polyethylenimine (PEI) method. HEK293suggested: NoneThe ACE2-HEK293 cells were seeded at a density of 10,000 cells per well into white 96-well cell culture microplate one day before transduction. ACE2-HEK293suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Briefly, a bolus intravenous injection of ACE2-Fc proteins (0.5mg/kg body weight) was performed in 10 weeks old female BALB/c mice. BALB/csuggested: RRID:IMSR_ORNL:BALB/cRl)Software and Algorithms Sentences Resources The IC50 values were determined by log(inhibitor) vs. response nonlinear regression fit analysis (GraphPad Prism). 2.7. 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:Nevertheless, the inclusion of immunoadhesin potentials of the antiviral may have caveats. While it may certainly boost immune clearance of the virus, such as through FcγR’s selective binding of clustered Fc, it may also elevate complement and cytokine responses to further aggravate the inflammation. Although these adverse side effects can be mitigated through modifications of the Fc domain, the ultimate therapeutic effects in the context of individual patients’ conditions can only be determined through rigorous clinical studies. With regard to drug toxicity, our mouse study of repeated doses of ACE2-Fc in mice had showed the biologic to be well tolerated for up to two months[13]. However, we cannot extrapolate that its will also be safe COVID-19 patients. As we consider it is not a simple neutralizing agent of the virus, its bifurcated ACE2 head groups can possibly trigger agglutination of the virus that can potentially aggravate the hypercoagulable state, making the drug less tolerable in these conditions. From the perspective of recombinant manufacturing, there are challenges ahead for the simple fact that ACE2-Fc is a large protein (∼130 kDa as a monomer and ∼260 kDa as a dimer). Furthermore, cocrystal structures of ACE2 with an inhibitor showed large movements of the two lobes as compared to the Apo structures[40], suggesting an intrinsic instability of ACE2 protein. Also of note is an earlier study by Lei et al using double mutations of His374 and His378 of the zinc-bin...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04335136 Completed Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) a… 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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 19, 20 and 21. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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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