Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis
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Abstract
COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.
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SciScore for 10.1101/2020.06.21.162396: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Approval to collect the tissue biopsies was obtained from the National Healthcare Group Domain-Specific Board of Singapore (DSRB Ref: D/11/228) and the institutional review board of the National University of Singapore (IRB Ref: 13-509).
Consent: Written consent was also obtained from the donors prior to tissue biopsies collection.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cell lines and Viruses: African green monkey kidney cells (Vero E6; ATCC Verosuggested: CLS Cat# 605372/p622_VERO, …SciScore for 10.1101/2020.06.21.162396: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Approval to collect the tissue biopsies was obtained from the National Healthcare Group Domain-Specific Board of Singapore (DSRB Ref: D/11/228) and the institutional review board of the National University of Singapore (IRB Ref: 13-509).
Consent: Written consent was also obtained from the donors prior to tissue biopsies collection.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cell lines and Viruses: African green monkey kidney cells (Vero E6; ATCC Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Primary screen with pre-treatment using ACE2-targeted inhibitors and 57-compound natural product libraries: Vero E6 cells were seeded onto 96-well plates (Corning) at a seeding density of 1×104 cells per 100 µl and incubated overnight prior to drug inhibitory assay. Vero E6suggested: NoneTo determine the cell viability profiles of the selected compounds, Vero E6 and HuH7 cells were seeded into 96-well plates at seeding densities of 1×104 cells and 7.5×103 cells per 100 µl, respectively. HuH7suggested: NoneSoftware and Algorithms Sentences Resources Approval to collect the tissue biopsies was obtained from the National Healthcare Group Domain-Specific Board of Singapore (DSRB Ref: D/11/228) and the institutional review board of the National University of Singapore (IRB Ref: 13-509). National Healthcaresuggested: NoneResults 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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SciScore for 10.1101/2020.06.21.162396: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Approval to collect the tissue biopsies was obtained from the National Healthcare Group Domain-Specific Board of Singapore ( DSRB Ref: D/11/228 ) and the institutional review board of the National University of Singapore ( IRB Ref: 13-509) . Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Pre-infection treatment of Vero E6 cells with citicoline and pravastatin sodium resulted in dose-dependent inhibition of SARS-CoV-2 ( Fig . 2a & 2b) , while a nondose-dependent inhibition of … SciScore for 10.1101/2020.06.21.162396: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Approval to collect the tissue biopsies was obtained from the National Healthcare Group Domain-Specific Board of Singapore ( DSRB Ref: D/11/228 ) and the institutional review board of the National University of Singapore ( IRB Ref: 13-509) . Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Pre-infection treatment of Vero E6 cells with citicoline and pravastatin sodium resulted in dose-dependent inhibition of SARS-CoV-2 ( Fig . 2a & 2b) , while a nondose-dependent inhibition of SARS-CoV-2 at lower concentrations was observed with tenofovir alafenamide ( Fig . 2c) . Vero E6suggested: CVCL_XD71This finding could not be recapitulated in HuH7 cells ( Fig . 2l ) most likely because the CC50 value of calcitriol was 4.7 μM in HuH7 cells ( Table S6) . HuH7suggested: CLS Cat# 300156/p7178_HuH7, CVCL_0336African green monkey kidney cells ( Vero E6; ATCC CRL-1586™) Verosuggested: ATCC Cat# CRL-1586, CVCL_0574Software and Algorithms Sentences Resources Approval to collect the tissue biopsies was obtained from the National Healthcare Group Domain-Specific Board of Singapore ( DSRB Ref: D/11/228 ) and the institutional review board of the National University of Singapore ( IRB Ref: 13-509) . National Healthcaresuggested: NoneResults 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 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 OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).
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SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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