PONE-D-25-32598Exploring Dolichos lablab Compounds as Potential Inhibitors for Fusion (F) Protein of Human Metapneumovirus (HMPV): A Systematic Computational ApproachPLOS ONE

Dear Dr. Morshed,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR: The submission reflects scientific relevance. However, some fundamental issues limit its quality for publication in the current form. For instance, the authors need to justify the significance of the study, relate it to the literature and identify the gap in the existing knowledge that this aims to satisfy, and ensure an adequate validation of the theoretical analysis. Again, what are the limitations of this study and how can the authors recommend future research on the study. Moreover, some concerns have been raised by the reviewers affecting certain sections of the study. Kindly pay a thorough attention to these and address them critically before resubmission.

==============================

Please submit your revised manuscript by Aug 30 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Yusuf Oloruntoyin Ayipo, Ph.D

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please note that PLOS One has specific guidelines on code sharing for submissions in which author-generated code underpins the findings in the manuscript. In these cases, we expect all author-generated code to be made available without restrictions upon publication of the work. Please review our guidelines at https://journals.plos.org/plosone/s/materials-and-software-sharing#loc-sharing-code and ensure that your code is shared in a way that follows best practice and facilitates reproducibility and reuse.

3. Please remove all personal information, ensure that the data shared are in accordance with participant consent, and re-upload a fully anonymized data set.

Note: spreadsheet columns with personal information must be removed and not hidden as all hidden columns will appear in the published file.

Additional guidance on preparing raw data for publication can be found in our Data Policy (https://journals.plos.org/plosone/s/data-availability#loc-human-research-participant-data-and-other-sensitive-data) and in the following article: http://www.bmj.com/content/340/bmj.c181.long.

4. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Additional Editor Comments :

The submission reflects scientific relevance. However, some fundamental issues limit its quality for publication in the current form. For instance, the authors need to justify the significance of the study, relate it to the literature and identify the gap in the existing knowledge that this aims to satisfy, and ensure an adequate validation of the theoretical analysis. Again, what are the limitations of this study and how can the authors recommend future research on the study. Moreover, some concerns have been raised by the reviewers affecting certain sections of the study. Kindly pay a thorough attention to these and address them critically before resubmission.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors report a systematic computational approach to screening compounds derived from a plant (Dolichos lablab) in search of an effective and safe antiviral capable of targeting the fusion protein of the human metapneumovirus to combat prevalence of resulting respiratory infections.

Manuscript requires a couple of corrections before acceptance:

First 2 paragraphs (particularly the first) of the introduction are missing key information and need reorganization. A good way to introduce is properly address respiratory infections and its burden, then viruses/ respiratory viruses. Also, we cannot address the issue of respiratory viruses without mentioning the likes of Influenza, SarsCoV2, and RSV as main causes.

In the sentence “Viruses have enzymes (polymerases) that help them with genome replication….”, authors should note that not all viruses have and/or use polymerases.

In the intro, kindly use hMPV or HMPV, not both.

In the sentence “Natural products, also referred to as plant derived phytochemical…”, authors should note that natural products encompass those obtained from microbes and animals too, not only plants. Therefore, “also referred to as” can’t be used in the description.

“…phytochemicals that prevent viral reproduction and penetration…” correction: phytochemicals that prevent viral entry and replication.

It is known that HMPV F protein has the pre-Fusion and post-Fusion confirmation, with the former usually targeted for antivirals. Authors should clearly state in the intro or method that pre-fusion conformation was used.

Results section clearly stated how the 86 compounds of DL were reduced to 16 after analysis. Authors however, did not clearly mention how and why the 3 selected compounds were preferred for some of the analyses done. For example, authors commended that the 3 selected compounds have higher binding affinity than Ribavirin, but there were compounds within the list that had much better binding affinity and weren’t selected.

Authors should be consistent with keywords. Any of (a) or (b) should have the same keywords throughout the manuscript except if properly replaced first.

(a) Table 1 - Ligands; Table 2 - Compound name; Table 3 - Compounds

(b) control, Ribavirin, Ribavirin (control).

It will be helpful if authors include Ribavirin as a control in all their analyses including in the tables shown for comparison.

“…but its clinical use is limited due to potential toxicity and lack of definitive efficacy in vivo.” Please include appropriate citation here.

Rewrite format of references 4 and 24.

References 48 and 52 are not related to the statements they are cited with. Kindly review source of information.

Figure 6C is missing the y-axis title.

Figure 6ABCD are missing the x-axis title.

Figure 7 is missing x-axis title.

Authors should note that the mode of action/ target of Ribavirin is not the F protein, but the viral polymerase. Or is the author suggesting that Ribavirin potentially targets F protein of HMPV too? This doesn’t affect the the analyses done with Ribavirin as a control.

Very important; Revise the quality of all the figures and ensure they meet submission standards.

Reviewer #2: Thank you for giving me the opportunity to review this manuscript titled "Exploring Dolichos lablab Compounds as Potential Inhibitors for Fusion (F) Protein of Human Metapneumovirus (HMPV): A Systematic Computational Approach."

Summary and Strengths

This study presents a computational pipeline to identify and evaluate potential phytochemical inhibitors from Dolichos lablab targeting the HMPV fusion (F) protein. The authors integrate molecular docking, ADMET profiling, bioactivity prediction, and molecular dynamics simulations to identify promising drug candidates—Brassinolide, Quercetin, and 2'-Hydroxygenistein.

Specific strengths include:

Clear Target Rationale: The manuscript justifies the selection of the HMPV fusion protein as a therapeutic target, citing its role in viral entry and lack of existing effective inhibitors.

Use of Natural Product Library: The use of Dolichos lablab, a plant with traditional medicinal uses and known pharmacological activity, strengthens the phytochemical selection rationale.

Comprehensive Methodology:

Docking was conducted with AutoDock Vina and PyRx, with thoughtful grid definition.

ADMET and Lipinski analyses were thorough, using multiple tools (SwissADME, admetSAR, pKCSM, Deep-PK).

MD simulations were performed for 100 ns using Desmond with detailed reporting of RMSD, RMSF, Rg, SASA, and bonding interactions.

The inclusion of MMGBSA free energy calculations via PRODIGY supports the thermodynamic favorability of binding.

Comparison to a Known Control (Ribavirin): The use of Ribavirin as a benchmark adds a point of reference, improving interpretability.

Limitations and Concerns

Despite its strengths, there are several critical limitations that must be addressed before publication:

1. Over-interpretation of Computational Data

No experimental validation: All conclusions are based solely on in silico data. While the manuscript acknowledges this in the discussion, the conclusions and abstract use definitive language (e.g., “effective inhibitor,” “demonstrated promising biological activity”) that overstates the evidence.

Suggested fix: Tone down the certainty in both the abstract and conclusion, making it clear these are hypothetical inhibitors pending in vitro validation.

2. Redundancy and Clarity

The manuscript is excessively repetitive. For instance, the results sections discussing RMSD, RMSF, and SASA repeat similar information already presented earlier. Much of this can be consolidated to improve readability.

There are also long sections describing every value in a table, which can be summarized more efficiently (e.g., in bullet format or comparative sentences).

3. Misplaced Emphasis in the Introduction

The introduction spends an inordinate amount of time reviewing unrelated viruses (e.g., monkeypox, hantavirus), which dilutes focus from HMPV.

Suggested fix: Remove extraneous background on unrelated viruses and expand the part discussing existing drug discovery efforts for HMPV or other respiratory paramyxoviruses.

4. Scientific Rigor in Docking Analysis

Docking poses and interactions are described, but the manuscript does not discuss if the docking site corresponds to a functionally important site on the F protein. Do the identified binding sites overlap with known neutralizing epitopes or fusion machinery?

Suggestion: Provide structural or functional context for the binding sites—are they in the prefusion region, HR1/HR2 domains, or fusion loop?

5. Lack of Controls and Benchmarking

While Ribavirin is used as a control for docking energy, there is no control for the MD simulations or MMGBSA scoring other than that. Including a known non-binder or random ligand could contextualize the stability of the selected hits better.

6. Clarity of Figures and Tables

Figures (e.g., Fig 2, 3, 6) are referenced in the text but not included in the version I reviewed. Ensure all visual elements are clear, labeled, and aligned with journal standards.

There is inconsistency in compound naming (e.g., CID_5282074 used twice for different compounds; possible typo).

Recommendation: Major Revisions

Given the extensive and well-structured computational approach, the manuscript presents interesting preliminary findings. However, I recommend major revisions before this work can be considered for publication. Specifically:

Revise the abstract and conclusion to avoid overstatements.

Reduce redundancy and improve clarity in the writing.

Improve discussion of the docking site's biological relevance.

Remove extraneous introductory background.

Ensure all compound IDs, docking poses, and data are accurately labeled and interpreted.

Consider additional computational validation (e.g., benchmarking with known ligands or adding entropy calculations).

If the authors can address these concerns and revise accordingly, the study may provide valuable insights for phytochemical-based antiviral drug discovery.

Reviewer #3: Dear Esteemed Editor,

I have examined the publication entitled Exploring Dolichos lablab Compounds as Potential Inhibitors for Fusion (F) Protein of Human Metapneumovirus (HMPV): A Systematic Computational Approach. This manuscript provides a thorough in silico examination of the potential inhibitory effects of phytocompounds derived from Dolichos lablab against the fusion (F) protein of human metapneumovirus (HMPV). The study is pertinent and opportune, as it addresses the unmet clinical need for effective antiviral therapies that specifically target HMPV. In order to identify and assess potential bioactive molecules, the authors have implemented a sequential computational methodology that includes ligand mining, molecular docking, ADMET and bioactivity screening, molecular dynamics (MD) simulation, and MMGBSA binding energy calculations.

However, I have pinpointed multiple areas requiring improvement prior to the manuscript's recommendation for publication

Strengths:

Scope and Relevance:

The study investigates the absence of targeted therapies for HMPV by conducting a screening of phytochemicals derived from Dolichos lablab. This is both novel and pertinent to the global respiratory health. It also incorporates ligand mining, molecular docking, ADMET profiling, bioactivity prediction, molecular dynamics (100 ns), and MMGBSA calculations, offering a comprehensive computational analysis.

The three compounds Brassinolide, Quercetin, and 2-Hydroxygenistein were prominently identified as leading candidates based on consistent outcomes from docking, ADMET, and MD simulations. Comprehensive tables and figures enhance transparency and replicability. The incorporation of MMGBSA values and protein-ligand interaction maps significantly augments scientific rigour.

Methodology:

The author utilized AutoDock Vina, SwissADME, admetSAR, Molinspiration, and Desmond effectively. They also made use of 100 ns molecular dynamics simulations, which are standard or above average in duration for preliminary in silico investigations.

The MMGBSA computation utilizing PRODIGY facilitates energetic validation of the docking results.

Presentation:

The methodologies and software are documented with their respective versions and settings.

Also, the data, tables and figures are appropriately labelled.

Suggestions:

Incorporate RMSD-based validation or re-docking of established inhibitors to ascertain docking precision

Please describe the filtering process.

Can you explain the necessity for subsequent experimental investigations in vitro and in vivo?

Also you should examine Lipinski's rule infractions and their impact on translational viability.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes:  Ikechukwu Kanu

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

PONE-D-25-32598R1Exploring Dolichos lablab Compounds as Potential Inhibitors for Fusion (F) Protein of Human Metapneumovirus (HMPV): A Systematic Computational ApproachPLOS ONE

Dear Dr. Morshed,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR: Many thanks to the authors for responding positively to the initial concerns. The revision has improved the quality of the submission. However, some grey areas still exist, and these require the authors’ significant attention through another round of revision. In lines 361-382, the authors have subtitled this section including the Table 4 as "Bioactivity". However, the only parameters presented there are TPSA, Molar volume and Rotatable bonds, which are understandably, physicochemical parameters for predicting polarity, size and flexibility of the molecules respectively. The rationale for tagging these "Bioactivity" remains confusing. Moreover, the data are mere predictions which require extensive experimental validation for certainty. I strongly recommend that these section be reconstructed and the superfluous statements be modified. The title should also indicate prediction since no experimental results have been provided. 

==============================

Please submit your revised manuscript by Oct 04 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Yusuf Oloruntoyin Ayipo, Ph.D

Academic Editor

PLOS ONE

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Many thanks to the authors for responding positively to the initial concerns. The revision has improved the quality of the submission. However, some grey areas still exist, and these require the authors’ significant attention through another round of revision. In lines 361-382, the authors have subtitled this section including the Table 4 as "Bioactivity". However, the only parameters presented there are TPSA, Molar volume and Rotatable bonds, which are understandably, physicochemical parameters for predicting polarity, size and flexibility of the molecules respectively. The rationale for tagging these "Bioactivity" remains confusing. Moreover, the data are mere predictions which require extensive experimental validation for certainty. I strongly recommend that these section be reconstructed and the superfluous statements be modified. The title should also indicate prediction since no experimental results have been provided.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

Exploring Dolichos lablab Compounds as Potential Inhibitors for Fusion (F) Protein of Human Metapneumovirus (HMPV): A Systematic Computational Approach

PONE-D-25-32598R2

Dear Dr. Morshed,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Yusuf Oloruntoyin Ayipo, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The submission is scientifically sound for publication in this title, and all the concerns raised by the respective reviewers regarding the manuscript quality have been satisfactorily addressed. I hereby recommend the manuscript for publication in the current version.

Reviewers' comments: