Extracellular vimentin as a target against SARS-CoV-2 host cell invasion
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Abstract
Infection of human cells by pathogens, including SARS-CoV-2, typically proceeds by cell surface binding to a crucial receptor. In the case of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) has been identified as a necessary receptor, but not all ACE2-expressing cells are equally infected, suggesting that other extracellular factors are involved in host cell invasion by SARS-CoV-2. Vimentin is an intermediate filament protein that is increasingly recognized as being present on the extracellular surface of a subset of cell types, where it can bind to and facilitate pathogens’ cellular uptake. Here, we present evidence that extracellular vimentin might act as a critical component of the SARS-CoV-2 spike protein-ACE2 complex in mediating SARS-CoV-2 cell entry. We demonstrate direct binding between vimentin and SARS-CoV-2 pseudovirus coated with the SARS-CoV-2 spike protein and show that antibodies against vimentin block in vitro SARS-CoV-2 pseudovirus infection of ACE2-expressing cells. Our results suggest new therapeutic strategies for preventing and slowing SARS-CoV-2 infection, focusing on targeting cell host surface vimentin.
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This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/4558519.
Main Claim & Relevance:
Extracellular vimentin might be critical to SARS-CoV-2 cell entry. These researchers demonstrated direct binding between vimentin and SARS-CoV-2 virus-like particles (VLPs) coated with SARS-CoV-2 spike protein. They also showed that antibodies against vimentin block in vitro SARS-CoV-2 pseudovirus infection by up to 80% in ACE2 expressing cell lines.
Are the findings strong, reliable, potentially informative, not informative, or misleading? Why?:
The findings are potentially informative. Immunostaining of human adult lung and adipose tissue was done to detect the presence of vimentin. The researchers showed that vimentin binds to SARS-CoV-2 virus-like …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/4558519.
Main Claim & Relevance:
Extracellular vimentin might be critical to SARS-CoV-2 cell entry. These researchers demonstrated direct binding between vimentin and SARS-CoV-2 virus-like particles (VLPs) coated with SARS-CoV-2 spike protein. They also showed that antibodies against vimentin block in vitro SARS-CoV-2 pseudovirus infection by up to 80% in ACE2 expressing cell lines.
Are the findings strong, reliable, potentially informative, not informative, or misleading? Why?:
The findings are potentially informative. Immunostaining of human adult lung and adipose tissue was done to detect the presence of vimentin. The researchers showed that vimentin binds to SARS-CoV-2 virus-like particles that contain SARS-CoV-2 spike 2 protein via dynamic light scattering (DLS) and atomic force microscopy (AFM).
The manuscript also mentions that there are now numerous studies implicating the role of vimentin in the binding and uptake of multiple different viruses, including the SARS virus.
How might these ideas presented by the main claims further knowledge of the COVID-19 pandemic?
They highlight extracellular vimentin as a potential therapeutic target against SARS-CoV-2 that could block the spread of COVID-19 and other potentially infectious diseases. Additionally, these researchers proposed a mechanism in which non-vimentin expressing cells can acquire vimentin released into the extracellular environment by neutrophil netosis.
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SciScore for 10.1101/2021.01.08.425793: (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 Primary rabbit anti-vimentin antibodies to the C-terminus at 1:200 were placed directly on tissues and left for overnight incubation in humidified chamber at 4°C. anti-vimentinsuggested: NoneNext, cells were incubated for 1h at RT with an Alexa Fluor 488-conjugated goat anti-rabbit secondary antibody at 1:1000. anti-rabbitsuggested: NoneChicken polyclonal IgY antibody (Novus Biologicals, Cat# NB300-223); (iii) primary anti-vimentin monoclonal antibody developed in rabbit immunized with a 17-residue synthetic peptide from a region within human vimentin amino acids 425-466 (Abcam, Cat# ab92547); (iv) … SciScore for 10.1101/2021.01.08.425793: (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 Primary rabbit anti-vimentin antibodies to the C-terminus at 1:200 were placed directly on tissues and left for overnight incubation in humidified chamber at 4°C. anti-vimentinsuggested: NoneNext, cells were incubated for 1h at RT with an Alexa Fluor 488-conjugated goat anti-rabbit secondary antibody at 1:1000. anti-rabbitsuggested: NoneChicken polyclonal IgY antibody (Novus Biologicals, Cat# NB300-223); (iii) primary anti-vimentin monoclonal antibody developed in rabbit immunized with a 17-residue synthetic peptide from a region within human vimentin amino acids 425-466 (Abcam, Cat# ab92547); (iv) Rabbit Monoclonal (Cell signaling Technology, Cat#5471); and (v) Ser56 N-terminus aa 1-80 (primary anti-vimentin polyclonal rabbit antibody; antibodies-online.com, Cat# ABIN6280132). antibodies-online.comsuggested: NoneExperimental Models: Cell Lines Sentences Resources +/+), vimentin-null fibroblast (mEF vim −/−), and human kidney epithelial cells HEK293T ACE2-transfected (Integral Molecular, Integral Cat# C-HA101). HEK293Tsuggested: NoneIn vitro infection of cells by VLP: HEK 293T-hsACE2 cell lines were used as infection hosts for SARS-CoV-2 GFP-reporter pseudovirus ( HEK 293T-hsACE2suggested: NoneSoftware and Algorithms Sentences Resources The total number of cells and the number of cells expressing GFP were manually counted in randomly selected 65 μm by 65 μm imaging windows in ImageJ. ImageJsuggested: (ImageJ, RRID:SCR_003070)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.
- 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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