Functional Peptides from SARS-CoV-2 Binding with Cell Membrane: From Molecular Dynamics Simulations to Cell Demonstration

Round 1

Reviewer 1 Report

Please see the attachment for details.

As indicated in my report, I detected in the manuscript plagiarism, several lines of material and metods:

Lines 95 to 108: The section 2.1.4 Dynamics light scattering is identical to the DLS section of the article of Bharatiya B. et al. Colloids and Surface B: Biointerfaces 2021, 199, 111551, page 111553.

Comments for author File: Comments.pdf

Author Response

Dear Reviewer,

Thank you very much for your effort to obtain the referee’s comments to our manuscript “Functional peptides of SARS-CoV-2 binding with cell membrane: from molecular dynamics simulations to cell demonstration” (Manuscript No.: cells-1713300). We appreciate the careful review and constructive suggestions from the editor and referees for improving our manuscript, and also important guiding to our research. We have revised our manuscript carefully according to the comments of editor and referees point by point. We improved the quality of figures. Furthermore, we improved the language, corrected the grammar, mis-spell and others. The revisions we have made were marked in red in the revised manuscript. It is our belief that the manuscript is substantially improved after making the suggested edits. We appreciate you very much if you would like to take the reconsideration of our manuscript for publishing in Cells.

 

Your consideration of our manuscript in your busy time is deeply appreciated, and we look forward to hearing from you.

 

With kind regards!

 

Sincerely yours,

Lei Liu

For all authors

 

 

Corresponding author: Lei Liu

Institute for Advanced Materials, Jiangsu University, Xuefu Road 301, Zhenjiang 212000, China,

Tel: +86 18206102793, Email: liul@ujs.edu.cn

Author Response File: Author Response.pdf

Reviewer 2 Report

From the paper, they have verified the interaction between the functional peptides from the SARS-CoV-2 and cell membrane, and also performed the in vitro/ in silico proved that peptides exhibited little membrane disruption. They illustrate the charge or hydrophobic residual amino acids of the functional peptides play the important role in cell membrane binding. The findings could provide the hints related to viral infection and also might pave the way for development of new materials based on peptides with membrane binding activity (including cancer targeting therapeutic vehicles?)

Article: Since this article belong to the Cell-Penetrating Peptides (CPPs) in Cancer: From Molecular Mechanisms to Applications in Diagnostic and Therapeutic Opportunities special issue, they should provide us the highlighting areas of medical application for cancer targeting or the testability of the hypothesis concerning cancer cells.

Review: Authors seems to lack of information how the two selected peptides (FP-1 and FP-2 in this study) correlate SARS-CoV-2 spike protein. Moreover, how does this affected by the different strains of SAR-CoV-2 which have different spike protein structures. They should also mention the highlighting areas of medical application of this two studied peptides for cancer targeting or the testability of the hypothesis concerning cancer cells. Since it's belong to the special issue in Cell-Penetrating Peptides (CPPs) in cancer, the author should mention in the introduction and discussion parts how this could be applied from molecular mechanism to applications in diagnostic and therapeutic opportunities.  

The author did not mention why the mouse fibroblast cell (L929) has been used in peptide cell membrane penetrating assay.

Specific comments

1)    The structure of FP-1 in figure1 A is not sharp and easy to be noticed. Perhaps, the color choice should be more contrast between FP-1 peptide and Spike protein (the purple chain)

2)    6VXX is the PDB Structure of the SARS-CoV-2 spike glycoprotein but in Fig.1 seems to lack of carbohydrate units.

3)    Figure 2 A is hard to read in detail. The resolution and sharpness of the text labeling should be improved.

4)    The text labeling in figure3 A and B should be more sharp and easier to be read.

5)    Are there any statistical analysis/test figure4 (A-F) to point out the significant different between the experimental groups.

6)    The column header of Table 1 should be improved to be easier for the readers. Perhaps, the rotation of header texts might help.

7)    Are there any statistical analysis/test figure5 (A-H) to point out the significant different between the experimental groups.

8)    Supplementary Materials in the manuscript should be count as figure 8.

9)    Supporting figure S1A should be improved in contrast and its quality.

10) The figure legend of Figure S2, page 1 line 13, should be specified as “the mouse fibroblast cell line (L929)” instead of “the mouse fibroblasts (L929)”

Author Response

Dear Reviewer 2,

Thank you very much for your effort to obtain the referee’s comments to our manuscript “Functional peptides of SARS-CoV-2 binding with cell membrane: from molecular dynamics simulations to cell demonstration” (Manuscript No.: cells-1713300). We appreciate the careful review and constructive suggestions from the editor and referees for improving our manuscript, and also important guiding to our research. We have revised our manuscript carefully according to the comments of editor and referees point by point. We improved the quality of figures. Furthermore, we improved the language, corrected the grammar, mis-spell and others. The revisions we have made were marked in red in the revised manuscript. It is our belief that the manuscript is substantially improved after making the suggested edits. We appreciate you very much if you would like to take the reconsideration of our manuscript for publishing in Cells.

 

Your consideration of our manuscript in your busy time is deeply appreciated, and we look forward to hearing from you.

 

With kind regards!

 

Sincerely yours,

Lei Liu

For all authors

 

 

Corresponding author: Lei Liu

Institute for Advanced Materials, Jiangsu University, Xuefu Road 301, Zhenjiang 212000, China,

Tel: +86 18206102793, Email: liul@ujs.edu.cn

Author Response File: Author Response.pdf

Reviewer 3 Report

The present report describes biophysical analyses related to peptides FP-1 and FP-2 interaction to synthetic membranes (i.e. POPG and DPPC). Results suggested that without causing membrane disruption, peptides FP-1 and FP-2, derived from the SARS-CoV-2 virus, interacted with lipid membranes. Structural specificity of such peptide-membrane interaction was provided, with specific charged and/or hydrophobic amino acids playing a role. The major conclusion was that peptides from SARS-CoV-2 virus envelope bind to synthetic membrane phospholipids. These are important findings as it provides clear experimental evidences that no receptor protein is necessary for the interaction of SARS-CoV-2 virus with biological membranes. Suggesting that effective pharmacological antiviral therapy should consider molecule(s) able to block both protein-protein and protein-phospholipids sites.  

 

Minor points:

The general quality of the manuscript will benefit from figures of higher resolution

Author Response

Dear Reviewer 3,

Thank you very much for your effort to obtain the referee’s comments to our manuscript “Functional peptides of SARS-CoV-2 binding with cell membrane: from molecular dynamics simulations to cell demonstration” (Manuscript No.: cells-1713300). We appreciate the careful review and constructive suggestions from the editor and referees for improving our manuscript, and also important guiding to our research. We have revised our manuscript carefully according to the comments of editor and referees point by point. We improved the quality of figures. Furthermore, we improved the language, corrected the grammar, mis-spell and others. The revisions we have made were marked in red in the revised manuscript. It is our belief that the manuscript is substantially improved after making the suggested edits. We appreciate you very much if you would like to take the reconsideration of our manuscript for publishing in Cells.

 

Your consideration of our manuscript in your busy time is deeply appreciated, and we look forward to hearing from you.

 

With kind regards!

 

Sincerely yours,

Lei Liu

For all authors

 

 

Corresponding author: Lei Liu

Institute for Advanced Materials, Jiangsu University, Xuefu Road 301, Zhenjiang 212000, China,

Tel: +86 18206102793, Email: liul@ujs.edu.cn

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The Authors in this revised versione improved the quality of the manuscript with respect to the first version.
I raccomand the publication of the paper in this version.

I suggest to change, in the caption of Figure 1D and in the section 2.1.2, "CD of the secondary structure of FP-1 and FP-2 in solution" in to "CD of FP-1 and FP-2 in solution"