A Comprehensive Analysis of Structural and Functional Changes Induced by SARS-CoV-2 Spike Protein Mutations

Round 1

Reviewer 1 Report

The prevention and control of infectious diseases will not be difficult providing no mutation was occurred in the main neutralizing antibodies eliciting proteins of virus, however, the opposite is true, especially in the cases of HIV, HCV, influenza virus, SARS-CoV-2, etc. The SARS-CoV-2 virus has sparked intense research on its spike protein, which is essential for viral entrance into host cells, as well as inducing neutralizing antibodies, and subsequent mutations of spike protein resulted in the continuous transmission of epidemic. The present manuscript summarized the effects of spike protein mutations, which will shed light on virology, pathogenicity, vaccines and drugs development. Before accepted for publication, several concerns should be well issued.

1.    The resolution of all the figures were low.

2.    The title of figure3, SARS-CoV2 should be SARS-CoV-2.

3.    There are many sentences repeat describe the variants with enhanced transmissibility and evading the immunoprotecting of current vaccines, and from time to time emphasize the importance of comprehending S protein on vaccine and drug development. All of these viewpoints are correct but should be avoided unnecessary repetition, so the manuscript needs further simplification.

4.    Too much guidelines or perspectives were given in the end of each part, which take so many spaces of the manuscript but failed to provide concrete or feasible suggestions.

5.    In my opinion, only the figure 8 was very meaningful, which should be corporately demonstrated with a table that summarizing all the known mutations as well as the effects of those mutations.

6.    As SARS-CoV-2 is well known, has far-reaching influence, has been invested a lot of research and has a high degree of popularization, the present manuscript provided few novel knowledge or systematic summary of information, many aspects of the content are passing by, and there is no in-depth discussion on mechanism or comparison.

Author Response

AUTHORS RESPONSES TO REVIEWERS COMMENTS

Dear Editor,

 

RE: Authors’ responses to reviewers’ comments

 

We wish to express our appreciation to the journal and the reviewers for the in-depth constructive comments, suggestions, and corrections, which have greatly improved the quality of our Manuscript. We carefully considered the latest set of comments raised and duly modified the new version of the Manuscript. A handful of grammatical corrections and typos, and a few places were improved for the Manuscript to read better.

 

 

 

Regards,

Aganze Gloire-Aime Mushebenge,

Corresponding Author

 

 

REVIEWER 1

General comment: The prevention and control of infectious diseases will not be difficult providing no mutation was occurred in the main neutralizing antibodies eliciting proteins of virus, however, the opposite is true, especially in the cases of HIV, HCV, influenza virus, SARS-CoV-2, etc. The SARS-CoV-2 virus has sparked intense research on its spike protein, which is essential for viral entrance into host cells, as well as inducing neutralizing antibodies, and subsequent mutations of spike protein resulted in the continuous transmission of epidemic. The present manuscript summarized the effects of spike protein mutations, which will shed light on virology, pathogenicity, vaccines and drugs development. Before accepted for publication, several concerns should be well issued.

 

Response to general comment:

We appreciate the reviewer's thoughtful comments on our manuscript regarding the effects of spike protein mutations in SARS-CoV-2. We completely agree with the reviewer and appreciate the insight.

 

Comment 1:    The resolution of all the figures were low.

 

Response 1: Thank you for the constructive comment.

We have removed most of the figures and have referenced accordingly the few remaining ones.

 

Comment 2:    The title of figure3, SARS-CoV2 should be SARS-CoV-2.

 

Response 2: Thank you, we have reflected the title to read as SARS-CoV-2.

 

Comment 3:    There are many sentences repeat describe the variants with enhanced transmissibility and evading the immunoprotecting of current vaccines, and from time to time emphasize the importance of comprehending S protein on vaccine and drug development. All of these viewpoints are correct but should be avoided unnecessary repetition, so the manuscript needs further simplification.

 

Response 3: Thank you, we have reviewed this comment, removed ambiguous and repeated sentences (as highlighted in yellow ink), thereby making the manuscript concise (red ink contains new edits) and void of repeats.

Lines 46-57 (page 3) of the introduction has been removed from the old version of the manuscript.

 

Comment 4:    Too much guidelines or perspectives were given in the end of each part, which take so many spaces of the manuscript but failed to provide concrete or feasible suggestions.

Response 4: Thank you for the constructive comment. Your comments are in order and have been improved on by removing some of the lines in 46-57 (page 2), 82-89 (page 3), 94-101 (page 3), 106-111 (page 3), 124-126 (page 3), 130-137 (page 4), 163-165 (page 5), 209-228 (page) in the old version of the manuscript.

 

Comment 5:    In my opinion, only the figure 8 was very meaningful, which should be corporately demonstrated with a table that summarizing all the known mutations as well as the effects of those mutations.

 

Response 5: Thank you for the constructive comment.

We have removed most of the figures and have referenced accordingly the few remaining ones. A clear version of the image was sent to the Editor.

 

 

Comment 6:    As SARS-CoV-2 is well known, has far-reaching influence, has been invested a lot of research and has a high degree of popularization, the present manuscript provided few novel knowledge or systematic summary of information, many aspects of the content are passing by, and there is no in-depth discussion on mechanism or comparison.

 

Response 6: We appreciate the reviewer's feedback on our manuscript focused on SARS-CoV-2. We acknowledge the significance of the virus and the extensive research that has been conducted on it. However, in our research group, we have employed in silico studies in the analysis of some identified novel SAR-CoV-2 inhibitors. We have inserted these novel studies in lines 50-67 (page 2) of the introduction in the updated version of the manuscript. However, we do not want to lose the focus of this present study which aims at providing an overview of the evolution and classification of spike protein mutations.

Reviewer 2 Report

The review by Mushebenge et al is well structured and covers a good range of topics related to COVID-19 and spike mutations. I have the following comments regarding the manuscript:

1) All the figures in the manuscript are reproduced from other literature. Has proper permission been taken from the respective authors? If so that must be mentioned and if not, then the figures need to replaced with original ones.

2) Many of the seminal and more recent publications on the host immune response to different COVID strains and their effects on severity have not been adequately cited.

3) There needs to be mention of the most recently emerging strains (Eris) of SAR-CoV-2.

Author Response

AUTHORS RESPONSES TO REVIEWER’S COMMENTS

Dear Editor,

 

RE: Authors’ responses to reviewers’ comments

 

We wish to express our appreciation to the journal and the reviewers for the in-depth constructive comments, suggestions, and corrections, which have greatly improved the quality of our Manuscript. We carefully considered the latest set of comments raised and duly modified the new version of the Manuscript. A handful of grammatical corrections and typos, and a few places were improved for the Manuscript to read better.

 

 

 

Regards,

Aganze Gloire-Aime Mushebenge,

Corresponding Author

 

 

REVIEWER 2

 

General comment: The review by Mushebenge et al is well structured and covers a good range of topics related to COVID-19 and spike mutations. I have the following comments regarding the manuscript:

 

Response to general comment: We sincerely appreciate the reviewer's positive assessment of our review on COVID-19 spike mutations. We value your insights and are eager to consider the comments raised regarding the manuscript. Your feedback is invaluable in helping us improve and refine the content for the benefit of the readers.

 

Comment 1: All the figures in the manuscript are reproduced from other literature. Has proper permission been taken from the respective authors? If so that must be mentioned and if not, then the figures need to replace with original ones.

 

Response 1: Thank you for your helpful observation. We have removed most of the figures and have referenced accordingly the few remaining ones.

 

Comment 2: Many of the seminal and more recent publications on the host immune response to different COVID strains and their effects on severity have not been adequately cited.

 

Response 2: Thank you for your thoughtful feedback.

The suggestion has been reflected in the introduction section lines 41-49 (page 1-2) in the updated version of the manuscript.

 

Comment 3: There needs to be mention of the most recently emerging strains (Eris) of SAR-CoV-2.

 

Response 3: Thank you for your valuable feedback. We have inserted this in the introduction section lines 78-81 (page 2) in the updated version of the manuscript.

Round 2

Reviewer 1 Report

All my concerns were well answered, I have no further comments.

Reviewer 2 Report

The revised manuscript addressed the concerns adequately.