PONE-D-24-19041Ligand-based pharmacophore modeling, virtual screening, and 2D quantitative structure-activity relationship performance on anti-Hepatitis B virus flavonolsPLOS ONE

Dear Dr. Mohebbi,

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Kind regards,

Nafees Ahemad

Academic Editor

PLOS ONE

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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

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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: No

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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 of the presented manuscript explored the anti-Hepatitis B potentiality of flavonol-based metabolites through combined ligand-based approaches. The study is considered relevant within the field of drug discovery. Few comments and suggestions are to be highlighted.

1. The abstract is better presented as single paragraph.

2. Authors should elaborate more on validating the pharmacophoric model through using more than one validation approach; cost analysis, decoy set and/or Fischer's method.

3. Chemical structures or even the SMILES strings of the identified hits should be presented. Additionally, aligning the identified hits with the deduced pharmacophoric model should be presented.

4. Finally, concerning the discussion/conclusion, authors are advised to elaborate more on the future of this work? What are the study limitations and what approaches could be conducted to further address them?

Reviewer #2: Title : It could be more concise e.g."Pharmacophore Modeling and QSAR Analysis of Anti-HBV Flavonols."

Abstract: Include a brief statement about the study's significance in relation to current HBV treatment options.

Methods: Certain technical terms may require clarification for readers who are not well-versed in the field. For example, a brief explanation of "Euclidean distance calculations" would be helpful.

Results: Some results lack adequate context or explanation. For example, when discussing the ROC curve, it would be beneficial to clarify what the specific AUC values indicate about the model's effectiveness. It is also suggested that the authors should provide a more thorough interpretation of the results, particularly regarding their implications for drug discovery.

Discussion: While the strengths of the models are highlighted, it is also important to address potential limitations and areas for improvement. I suggest that a paragraph discussing the study's limitations, such as possible biases in the screening process or the limited diversity of the flavonoids examined should be added.

General Comments

Strengths:

The manuscript conducts a comprehensive investigation into the pharmacological potential of flavonols against HBV, offering valuable insights to the field. However, there are grammatical errors and awkward phrasing throughout the text and a thorough proofreading is therefore highly recommended to identify any remaining errors and improve overall clarity.

Conclusion

The study presents significant findings that could enhance the understanding of anti-HBV compounds and contribute to the development of new therapeutic strategies. But focusing on clarity, critical analysis of results, and comprehensive proofreading will improve the manuscript's overall quality.

Recommendation

I consider it appropriate for publication in PLoS ONE, provided the authors address the comments and suggestions mentioned above.

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Reviewer #1: Yes: Khaled M Darwish

Reviewer #2: No

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Pharmacophore Modeling and QSAR Analysis of Anti-HBV Flavonols

PONE-D-24-19041R1

Dear Dr. Mohebbi,

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.

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Kind regards,

Nafees Ahemad

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: (No Response)

Reviewer #2: All comments have been addressed

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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: (No Response)

Reviewer #2: Yes

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

Reviewer #1: (No Response)

Reviewer #2: Yes

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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: (No Response)

Reviewer #2: Yes

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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: (No Response)

Reviewer #2: Yes

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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)

Reviewer #2: (No Response)

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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: Yes: Khaled M. Darwish

Reviewer #2: Yes: Professor Olorunfemi A. Eseyin

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