-->PONE-D-25-42057-->-->An Evaluation of Roluperidone as a Promising Repurposing Candidate for Alzheimer’s Disease-->-->PLOS ONE

Dear Dr. Al-Amin,

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.

==============================-->-->Researchers performed an extensive virtual screening to reconsider different drugs likely linked to Alzheimer's disease. They refined these to nine molecules, ultimately identifying Roluperidone as a prospective candidate for Alzheimer's disease treatment. This screening technique presented literature examples of both virtual screening and the in vitro experimental efficacy of particular drugs in preventing Alzheimer's disease. At this point, more extensive screening may be performed, and research previously assessed in vitro or in vivo against AD could be examined and integrated into the article.-->-->==============================

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We look forward to receiving your revised manuscript.

Kind regards,

Zeynep Ozdemir

Academic Editor

PLOS ONE

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Additional Editor Comments:

Researchers performed an extensive virtual screening to reconsider different drugs likely linked to Alzheimer's disease. They refined these to nine molecules, ultimately identifying Roluperidone as a prospective candidate for Alzheimer's disease treatment. This screening technique presented literature examples of both virtual screening and the in vitro experimental efficacy of particular drugs in preventing Alzheimer's disease. At this point, more extensive screening may be performed, and research previously assessed in vitro or in vivo against AD could be examined and integrated into the article. Furthermore, necessary revisions must be implemented in accordance with the referee's recommendations.

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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

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

Reviewer #1: 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

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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: 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: The manuscript entitled “An Evaluation of Roluperidone as a Promising Repurposing Candidate for Alzheimer’s Disease” has been reviewed.

The manuscript presents a well-designed study in the field of computational chemistry. I recommend publishing this manuscript after minor revision:

- The manuscript should be checked for spelling errors, as there are many misspellings and errors.

-In the introduction, the computer-aided drug design section was briefly explained with a very good introduction, however, a figure explaining the structure and ligand-based design could be added.

- Abbreviations should be written according to the same standards.

Abbreviations that appear as "Ach" should be corrected to "ACh."

IC50 spellings should be written according to the rules.

Words that should be italicized should be corrected. (For example, in vitro, etc.)

- Figure and supporting information citations must be written correctly. In many places, citations were indicated as Figure X and SX.

- It can be explained in detail which tools they use in fingerprint calculations.

- The docking method was quite simple and straightforward. However, the 25x25x25 area determined during the docking process should be explained in detail.

- The reasons for selecting these drugs based on the similarity graph in 3.3.1 should be detailed. The basis for the machine learning elimination, which parameters stood out, and so on, should be specified.

- Bond lengths are also given in Table 3. The study focuses on other important aspects, but bond lengths are not mentioned. Are physicochemical parameters used in the calculation, or where are they important for comparison? If they are not important, what is the purpose of including them on the table?

- The molecular dynamics studies were well interpreted. The tools used were different, but are the underlying equations in their calculations the same? This needs to be explained.

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-->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

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NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

An Evaluation of Roluperidone as a Promising Repurposing Candidate for Alzheimer’s Disease: A Computational Investigation

PONE-D-25-42057R1

Dear Dr. Al-Amin,

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,

Zeynep Ozdemir

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All comments have been addressed.

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

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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: Yes

**********

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

Reviewer #1: Yes

**********

-->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)

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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: 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)

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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: No

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