The Analyses of High Infectivity Mechanism of SARS-CoV-2 and Its Variants
, Fangyin Dai 1, Fengxiu Zhang 5 and Guangxian Zhang 1,2,*Round 1
Reviewer 1 Report
Please correct "Coulombs" into "Coulomb's"
The authors have developed a theoretical explanation of the affinity of Spike for ACE2 based on biophysical (elecrostatic) features of the Spike protein, and have validated this on 4 VOCs (plus a minor Alpha variant). It would be interesting to expand the model to 2 VOIs (mu and lambda) and to so-called Delta Plus (AY.1 and AY.2, additionally harbouring K417N). I only have minor suggestions for the text.
line 24 : Please delete from abstract the sentence : ". Then, SARS-CoV-2 and its variants had enhanced infectivity"
line 41: please correct "the PRRA sequence exists in SARS-CoV-2, so the SARS-CoV-2 spike protein cleaves more easily". At the top of this reviewer head, the authors are attempting to say that SARS-CoV-2 Spike has a second furin-cleavage site (FCS) compared to SARS-CoV Spike.
Please replace Sp1 and Sp2 with S1 and S2 subunits (more commonly used abbreviations.).
Author Response
Dear editors and reviewers,
Thank you for your careful review, helpful comments, and constructive suggestions, which have significantly improved the presentation of our manuscript. We have carefully considered all comments from the editors and reviewers and revised our manuscript accordingly. In the following sections, we have carried out the corrections and summarized our responses to each comment from the editors. Please find the following detailed responses.
Please correct "Coulombs" into "Coulomb's"
Response: Thank you for pointing out this problem in our manuscript, we are appreciative for your suggestions. We have revised "Coulombs" into "Coulomb's", the information are presented in the part of abstract (on line 25 in page 1).
The authors have developed a theoretical explanation of the affinity of Spike for ACE2 based on biophysical (elecrostatic) features of the Spike protein, and have validated this on 4 VOCs (plus a minor Alpha variant). It would be interesting to expand the model to 2 VOIs (mu and lambda) and to so-called Delta Plus (AY.1 and AY.2, additionally harbouring K417N). I only have minor suggestions for the text.
Response: Thank you for the encouraging comments and suggestions. We have added the analyzed data of the two VOIs and Delta Plus based on the review comments, and the information are presented in Table 5 of page 5.
line 24 : Please delete from abstract the sentence : ". Then, SARS-CoV-2 and its variants had enhanced infectivity"
Response: Thank you for your suggestions. We have deleted the content presented on line 24 in page 1.
line 41: please correct "the PRRA sequence exists in SARS-CoV-2, so the SARS-CoV-2 spike protein cleaves more easily". At the top of this reviewer head, the authors are attempting to say that SARS-CoV-2 Spike has a second furin-cleavage site (FCS) compared to SARS-CoV Spike.
Response: Thank you pointing out this problem in our manuscript. We have revised this sentence on line 41 in page 1.
Please replace Sp1 and Sp2 with S1 and S2 subunits (more commonly used abbreviations.).
Response: Thank you very much for your comments and suggestions. We have replaced all Sp1 and Sp2 into S1 and S2. The modifications are highlighted in red in the revised manuscript.
Many thanks for your kind help. We sincerely hope that this revised manuscript has addressed all editors’ and reviewers’ warm comments and suggestions. We sincerely hope our revised manuscript will meet with approval. Once again, thank you very much for your comments and suggestions.
Best wishes.
First author: Dr. Yonghua Lu and corresponding author Prof. Dr. Guangxian Zhang
2-Nov.-2021
Author Response File: 
Author Response.docx
Reviewer 2 Report
Dear authors
Your contribution is very interesting since it reports new speculation based on the physical properties of the affinities between the Sp (SRAS-CoV-2) and its human receptor (ACE-2).
Although the paper is well presented, I think some information should be added regarding:
1- The physical and chemical interactions between SARS-CoV2 and ACE-2;
2- Structures of both ACE-2 and SARS-CoV-2
3- The results should be further discussed by adding more details based on recent studies
4- Possible application of such speculation in other fields (oncology, HIV, ....) should be added as perpsectives.
Author Response
Dear editors and reviewers,
Thank you for your careful review, helpful comments, and constructive suggestions, which have significantly improved the presentation of our manuscript. We have carefully considered all comments from the editors and reviewers and revised our manuscript accordingly. In the following sections, we have carried out the corrections and summarized our responses to each comment from the editors. Please find the following detailed responses.
1- The physical and chemical interactions between SARS-CoV2 and ACE-2;
Response: We are appreciative of your profound suggestions. We think the interaction between high molecules belongs to physical interaction, then in our opinion, we think there is no chemical interaction between SARS-CoV2 and ACE-2. The main interaction between SARS-CoV2 and ACE-2 is coulomb interaction. Certainly, after the SARS CoV-2 combined the ACE2, there were hydrogen bonding forces, polar groups, and van der Waals forces between SARS CoV-2 and ACE2. We have added this statement in the revised manuscript.
2- Structures of both ACE-2 and SARS-CoV-2
Response: Thank you very much for your specific comments. We would like to test and obtain protein structure information ourselves, but unfortunately, we do not have this kind of plotting software. Therefore, in the revised manuscript, we have quoted the structure information about SARS-CoV-2, SARS-CoV and ACE2, and the referenced references are added between line 52 and 54 in page 2, the readers can refer these papers.
3- The results should be further discussed by adding more details based on recent studies
Response: Thank you for pointing out this problem in our manuscript, we are appreciative for your suggestions. We have added the content of the expanded model to 2 VOIs (mu and lambda) and Delta Plus, and the information are listed in Table 5 of page 5.
4- Possible application of such speculation in other fields (oncology, HIV, ....) should be added as perpsectives.
Response: We thank the reviewer for the forward-looking comments and suggestions. We have updated and introduced the content about possible application of speculation in other fields into our manuscript (on line 164-170), and hope that this will stimulate future studies on this interesting question.
Many thanks for your kind help. We sincerely hope that this revised manuscript has addressed all editors’ and reviewers’ warm comments and suggestions. We sincerely hope our revised manuscript will meet with approval. Once again, thank you very much for your comments and suggestions.
Best wishes.
First author: Dr. Yonghua Lu and corresponding author Prof. Dr. Guangxian Zhang
2-Nov.-2021
Author Response File: Author Response.docx
