Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by lactoferricin
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
In addition to vaccines, there is an urgent need for supplemental antiviral therapeutics to dampen the persistent COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The transmembrane protease serine 2 (TMPRSS2), that is responsible for proteolytic priming of the SARS-CoV-2 spike protein, appears as a rational therapeutic target. Accordingly, selective inhibitors of TMPRSS2 represent potential tools for prevention and treatment of COVID-19. Previously, we identified the human milk glycoprotein lactoferrin as a natural inhibitor of plasminogen conversion to plasmin, a serine protease homologous to TMPRSS2. Here, we tested whether lactoferrin and lactoferricin, a biologically active natural peptide produced by pepsin-mediated digestion of lactoferrin, together with synthetic peptides derived from lactoferrin, were able to block TMPRSS2 and SARS-CoV-2 infection. Particularly, we revealed that both lactoferricin and the N-terminal synthetic peptide pLF1 significantly inhibited: i) proteolytic activity of TMPRSS2 and plasmin, ii) proteolytic processing of the SARS-CoV-2 spike protein, and iii) SARS-CoV-2 infection of SARS-CoV-2-permissive cells. Thus, natural and synthetic peptides derived from lactoferrin represent feasible candidates for supporting prevention and treatment of COVID-19.
Article activity feed
-
-
SciScore for 10.1101/2021.12.20.473447: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The reaction mixtures were analyzed by immunoblotting with a specific anti-S-protein monoclonal antibody (mAb) (NovusBio, Littleton, CO). anti-S-proteinsuggested: NoneExperimental Models: Cell Lines Sentences Resources SARS-CoV-2 infection and In-Cell ELISA: The African green monkey kidney-derived Vero cells (ATCC CCL-81TM) were seeded into 96-well flat-bottom plates (1×104 cells, 80 μl/well) in Dulbecco’s Modified Eagle’s medium (DMEM), high glucose, with GlutaMAX and sodium pyruvate … SciScore for 10.1101/2021.12.20.473447: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The reaction mixtures were analyzed by immunoblotting with a specific anti-S-protein monoclonal antibody (mAb) (NovusBio, Littleton, CO). anti-S-proteinsuggested: NoneExperimental Models: Cell Lines Sentences Resources SARS-CoV-2 infection and In-Cell ELISA: The African green monkey kidney-derived Vero cells (ATCC CCL-81TM) were seeded into 96-well flat-bottom plates (1×104 cells, 80 μl/well) in Dulbecco’s Modified Eagle’s medium (DMEM), high glucose, with GlutaMAX and sodium pyruvate (Gibco/Thermo Fisher Scientific, Waltham, MA USA) supplemented with 10% fetal calf serum (FCS, Biowest, Nuaillé, France), 1% MEM non-essential amino acids solution, 100 U/mL penicillin and 100 μg/mL streptomycin (all latter from Gibco/Thermo Fisher Scientific). Verosuggested: RRID:CVCL_ZW93)Recombinant DNA Sentences Resources The sequences of the 19-amino-acids-long synthetic peptides were as follows: GRRRSVQWCAVSQPEATKC (the N-terminal pLF1, residues 1-19), EDAIWNLLRQAQEKFGKDK (the middle pLF2, residues 264-282), NLKKCSTSPLLEACEFLRK (the C-terminal pLF3, residues 674-692), and NFRTKSCPLELAKELKLCS (pCTR, a scrambled variant of pLF3). pLF1suggested: NonepCTRsuggested: NonepLF3suggested: 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: 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.
Results from scite Reference Check: We found no unreliable references.
-