Dear Dr Iwami,

Thank you for submitting this revised version of your manuscript entitled "Quantitative comparison of SARS-CoV-2, MERS-CoV and SARS-CoV dynamics: Implications for therapy" for consideration as a Research Article by PLOS Biology.

Your revisions have now been evaluated by the PLOS Biology editorial staff, and by the Academic Editor, and I'm writing to let you know that we would like to send your submission out for re-review.

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Kind regards,

Roli Roberts

Roland G Roberts, PhD,

Senior Editor

PLOS Biology

Dear Shingo,

Thank you for submitting your revised Research Article entitled "Quantitative comparison of SARS-CoV-2, MERS-CoV and SARS-CoV dynamics: Implications for therapy" for publication in PLOS Biology. I've now obtained advice from two of the original reviewers and have discussed their comments with the Academic Editor. Please note that reviewer #3 is the person who had told us that they had reviewed your study for another journal, but to whose comments you responded. Reviewer #2 is the original PLOS Biology reviewer #2. Reviewer #1 was not able to re-review.

Based on the reviews, we will probably accept this manuscript for publication, assuming that you will modify the manuscript to address the remaining points raised by the reviewers. Please also make sure to address the data and other policy-related requests noted at the end of this email.

IMPORTANT:

a) Please attend to the remaining requests from reviewer #3.

b) Please update your co-author's funding information (as discussed in our email conversation).

c) Please change your title to something that makes it clear that this is a modelling study, and that reduces the emphasis on implications for therapy. We suggest the following: "A quantitative model to compare within-host SARS-CoV-2, MERS-CoV and SARS-CoV dynamics provides insights into the pathogenesis of SARS-CoV-2"

d) Please address my Data Policy requests (see further down) by supplying the data and/or code that underlies the Figures.

We expect to receive your revised manuscript within two weeks. Your revisions should address the specific points made by each reviewer.

To submit your revision, please go to https://www.editorialmanager.com/pbiology/ and log in as an Author. Click the link labelled 'Submissions Needing Revision' to find your submission record. Your revised submission must include the following:

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https://journals.plos.org/plosbiology/s/supporting-information  

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Please do not hesitate to contact me should you have any questions.

Best wishes,

Roli

Roland G Roberts, PhD,

Senior Editor,

rroberts@plos.org,

PLOS Biology

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DATA POLICY:

You may be aware of the PLOS Data Policy, which requires that all data be made available without restriction: http://journals.plos.org/plosbiology/s/data-availability. For more information, please also see this editorial: http://dx.doi.org/10.1371/journal.pbio.1001797 

Note that we do not require all raw data. Rather, we ask that all individual quantitative observations that underlie the data summarized in the figures and results of your paper be made available in one of the following forms:

1) Supplementary files (e.g., excel). Please ensure that all data files are uploaded as 'Supporting Information' and are invariably referred to (in the manuscript, figure legends, and the Description field when uploading your files) using the following format verbatim: S1 Data, S2 Data, etc. Multiple panels of a single or even several figures can be included as multiple sheets in one excel file that is saved using exactly the following convention: S1_Data.xlsx (using an underscore).

2) Deposition in a publicly available repository. Please also provide the accession code or a reviewer link so that we may view your data before publication. 

Regardless of the method selected, please ensure that you provide the individual numerical values that underlie the summary data displayed in the following figure panels as they are essential for readers to assess your analysis and to reproduce it: data for Fig S1, and data or code needed to generate Figs 1, 2ABCDEF, 3ABCDEF, S2ABCDEF, S3ABCDEF, S4ABC, S5ABCDEF, S6ABCDEF, S7. NOTE: the numerical data provided should include all replicates AND the way in which the plotted mean and errors were derived (it should not present only the mean/average values).

IMPORTANT: Please also ensure that figure legends in your manuscript include information on where the underlying data can be found, and ensure your supplemental data file/s has a legend.

Please ensure that your Data Statement in the submission system accurately describes where your data can be found.

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REVIEWERS' COMMENTS:

Reviewer #2:

The revised paper with much more patient data does help to address my concerns. Also, the more detailed explanations of the roles of different drug types now make sense to me. I have no further comments.

Reviewer #3:

I thank the authors for their thorough responses to my previous comments. I think the manuscript is more focused and more clearly states what the modelling can show.

I just have two remaining comments:

1. For the target cell models it is mentioned that the parameters implicitly include the immunity. Do these parameters (delta for example as mentioned in the discussion) change over time. If not, they are missing an important thing that immunity does to control infection which is proliferate over time. Could the authors please comment on this.

2. I would still like to see a little more discussion in line 306-313 on the endpoints used in trials that are generally not viral, and how what it is that is important for the drugs to be able to do (I would think reduce severity and death) and how this is not what is discussed in this paper.

Dear Shingo,

On behalf of my colleagues and the Academic Editor, Bill Sugden, I'm pleased to say that we can in principle offer to publish your Research Article "A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2" in PLOS Biology, provided you address any remaining formatting and reporting issues. These will be detailed in an email that will follow this letter and that you will usually receive within 2-3 business days, during which time no action is required from you. Please note that we will not be able to formally accept your manuscript and schedule it for publication until you have made the required changes.

Please take a minute to log into Editorial Manager at http://www.editorialmanager.com/pbiology/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process.

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We also ask that you take this opportunity to read our Embargo Policy regarding the discussion, promotion and media coverage of work that is yet to be published by PLOS. As your manuscript is not yet published, it is bound by the conditions of our Embargo Policy. Please be aware that this policy is in place both to ensure that any press coverage of your article is fully substantiated and to provide a direct link between such coverage and the published work. For full details of our Embargo Policy, please visit http://www.plos.org/about/media-inquiries/embargo-policy/.

Thank you again for supporting Open Access publishing. We look forward to publishing your paper in PLOS Biology. 

Sincerely,

Roli

Roland G Roberts, PhD 

Senior Editor 

PLOS Biology