Atazanavir, Alone or in Combination with Ritonavir, Inhibits SARS-CoV-2 Replication and Proinflammatory Cytokine Production
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Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease (COVID-19) would allow the rapid implementation of potentially life-saving procedures. The major protease (Mpro) of SARS-CoV-2 is considered a promising target, based on previous results from related CoVs with lopinavir (LPV), an HIV protease inhibitor.
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SciScore for 10.1101/2020.04.04.020925: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources The purity of human monocytes was above 95%, as determined by flow cytometric analysis (FACScan; Becton Dickinson) using anti-CD3 (BD Biosciences) and anti-CD16 (Southern Biotech) monoclonal antibodies. anti-CD3suggested: Noneanti-CD16suggested: NoneExperimental Models: Cell Lines Sentences Resources SARS-CoV-2 was prepared in Vero E6 cells from an isolate contained on a nasopharyngeal swab obtained from a confirmed case in Rio de Janeiro, Brazil. Vero E6suggested: RRID:CVCL_XD71)Yield-reduction assay: Cells were infected with a multiplicity of infection (MOI) of 0.01. Vero or A549 cells were infected at … SciScore for 10.1101/2020.04.04.020925: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources The purity of human monocytes was above 95%, as determined by flow cytometric analysis (FACScan; Becton Dickinson) using anti-CD3 (BD Biosciences) and anti-CD16 (Southern Biotech) monoclonal antibodies. anti-CD3suggested: Noneanti-CD16suggested: NoneExperimental Models: Cell Lines Sentences Resources SARS-CoV-2 was prepared in Vero E6 cells from an isolate contained on a nasopharyngeal swab obtained from a confirmed case in Rio de Janeiro, Brazil. Vero E6suggested: RRID:CVCL_XD71)Yield-reduction assay: Cells were infected with a multiplicity of infection (MOI) of 0.01. Vero or A549 cells were infected at densities of 5 × 105 cells/well. A549suggested: NoneVirus titration: Monolayers of Vero cells (2 × 104 cell/well) in 96-well plates were infected with a log-based dilution of supernatants containing SARS-CoV-2 for 1h at 37°C. Verosuggested: RRID:CVCL_ZW93)Software and Algorithms Sentences Resources ELISA assays were purchased from R&D Bioscience. R&D Biosciencesuggested: (UMD Bioprocess Scale-Up Facility, RRID:SCR_012703)Molecular docking: ATV (PubChem CID: 148192) and LPV (PubChem CID: 92727) were used as inhibitors of the SARS-CoV-2 Mpro. PubChemsuggested: (PubChem, RRID:SCR_004284)Molecular docking experiments were performed with DOCK 6.946 for identifying the binding site of the Mpro. DOCKsuggested: (DOCK, RRID:SCR_000128)Molecular dynamics: Since the tertiary structure (3D) of the SARS-CoV-2 Mpro is a homodimer, we focused the molecular dynamics only one chain, henceforward chain A. Molecular dynamics calculations were performed using NAMD 2.949 and Charmm27* force field50 at pH 7, i.e., with deprotonated Glu and Asp, protonated Arg and Lys, and neutral His with a protonated Nε atom. NAMDsuggested: (NAMD, RRID:SCR_014894)The dose-response curves used to calculate EC50 and CC50 values were generated by variable slope plot from Prism GraphPad software 8.0. Prism GraphPadsuggested: 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 did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 22. 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.
- 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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