Host PDZ-containing proteins targeted by SARS-Cov-2
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Abstract
Small linear motif targeting protein interacting domains called PDZ have been identified at the C-terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins E, 3a, and N. Using a high-throughput approach of affinity-profiling against the full human PDZome, we identified sixteen human PDZ binders of SARS-CoV-2 proteins E, 3A and N showing significant interactions with dissociation constants values ranging from 3 μM to 82 μM. Six of them (TJP1, PTPN13, HTRA1, PARD3, MLLT4, LNX2) are also recognized by SARS-CoV while three (NHERF1, MAST2, RADIL) are specific to SARS-CoV-2 E protein. Most of these SARS-CoV-2 protein partners are involved in cellular junctions/polarity and could be also linked to evasion mechanisms of the immune responses during viral infection. Seven of the PDZ-containing proteins among binders of the SARS-CoV-2 proteins E, 3a or N affect significantly viral replication under knock-down gene expression in infected cells. This PDZ profiling identifying human proteins potentially targeted by SARS-CoV-2 can help to understand the multifactorial severity of COVID19 and to conceive effective anti-coronaviral agents for therapeutic purposes.
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SciScore for 10.1101/2021.02.01.429176: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. 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 Cells: A549 cells stably expressing ACE2 (A549-ACE2, kindly provided by Dr. Olivier Schwartz), were propagated at 37°C, 5% CO2 in DMEM with L-glutamine (Gibco) supplemented with 10% FBS, penicillin-streptomycin and 20 μg/mL blasticidin S. A549suggested: NoneIt was propagated once in Vero-E6 cells. siRNA: Virus infections: For infections, the cell culture medium was replaced with virus inoculum (MOI 0.1 PFU/cell) and incubated for one … SciScore for 10.1101/2021.02.01.429176: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. 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 Cells: A549 cells stably expressing ACE2 (A549-ACE2, kindly provided by Dr. Olivier Schwartz), were propagated at 37°C, 5% CO2 in DMEM with L-glutamine (Gibco) supplemented with 10% FBS, penicillin-streptomycin and 20 μg/mL blasticidin S. A549suggested: NoneIt was propagated once in Vero-E6 cells. siRNA: Virus infections: For infections, the cell culture medium was replaced with virus inoculum (MOI 0.1 PFU/cell) and incubated for one hour at 37°C, 5% CO2. Vero-E6suggested: 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.
- 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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