PONE-D-24-19810Screening of phytoconstituents from Bacopa monnieri (L.) Pennell and Mucuna pruriens (L.) DC. to identify potential inhibitors against Cerebroside Sulfotransferase.PLOS ONE

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Rajesh Kumar Pathak, Ph.D.

Academic Editor

PLOS ONE

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Additional Editor Comments:

The manuscript entitled “Screening of phytoconstituents from Bacopa monnieri (L.) Pennell and Mucuna pruriens (L.) DC. to identify potential inhibitors against Cerebroside Sulfotransferase” has undergone extensive review. Based on the reviewers' comments and suggestions, the authors need to revise the manuscript thoroughly to enhance its quality and readability.

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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

Reviewer #3: Yes

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

Reviewer #1: N/A

Reviewer #2: Yes

Reviewer #3: N/A

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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

Reviewer #3: 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: Yes

Reviewer #3: Yes

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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: Some points for revision are as follows;

1. Check all full stop placed before and after reference citation.

2. Better to write all amino acids with their position as Lys82 rather than LYS82.

3. Check all abbreviations such as TPSA, HBA, HBD, and others not defined.

4. What is meaning of Predicted toxicity class 1-6? (which one is good, better, best, or worst?)

5. In table 3, column interaction type and distance not represented a well and meaningful way. Instead of these column, add a column H-bonding residues.

6. In abstract, sentence "These compounds bound to the active site pocket of CST by interacting with LYS82, LYS85, SER89, TYR176, PHE170, PHE177 in the binding pocket. " say something but residues in table 3 indicate something different. Check and revise.

7. Check capital and small case. use an uniform style. case: upper panel Lower panel

8. Check this sentence "The average intramolecular hydrogen bonds for free CST, CST-GC, IMPHY001534, CST-IMPHY004141, CST-IMPHY009537, and IMPHY014836 were 175.37, 186.13, 172.20, 180.62, 174.09, and 175.8, respectively"

9. It will be more better to use compound name rather than ID as there exists different ID for the same compound in different chemical databases.

10. In table 5, interaction type and distance not represented in meaningful way. Instead of these column, add a column H-bonding residues.

11. There are many more figures, and many subfigures placed on a figure. I suggest you to place some figures as supplementary. Also, improve the quality of text and clarity of figures.

Reviewer #2: The paper titled "Screening of phytoconstituents from Bacopa monnieri (L.) Pennell and Mucuna pruriens (L.) DC. to identify potential inhibitors against Cerebroside Sulfotransferase" presents a comprehensive computational study aimed at identifying potential inhibitors against Cerebroside Sulfotransferase (CST) as a therapeutic target for metachromatic leukodystrophy (MLD). The study employs a multistep virtual screening approach, molecular dynamics simulations, and pharmacokinetic analyses to identify four phytoconstituents with potential inhibitory activity against CST. The paper is well-structured and provides detailed insights into each step of the computational methodology, along with thorough results and discussion sections.

The introduction provides a thorough overview of MLD, its pathophysiology, and current therapeutic approaches, which contextualizes the significance of identifying CST inhibitors. However, it would be beneficial to provide more context on the existing challenges and limitations in developing CST inhibitors, particularly focusing on the lack of experimental structural data for CST, which necessitates the use of computational modeling and virtual screening approaches.

The methodology section is comprehensive and well-described. It provides sufficient details on protein preparation, ligand screening, molecular docking, pharmacokinetic analyses, MM-PB/GBSA calculations, molecular dynamics simulations, and cross-target identification. However, it would be helpful to include the programming script used for each step of the computational analysis, as this can impact reproducibility and compatibility with future studies.

The results section presents a detailed analysis of the screening process, including the identification of top hits based on binding scores, pharmacokinetic properties, MM-PB/GBSA calculations, molecular dynamics simulations, and cross-target identification.

The discussion section effectively interprets the findings in the context of the study objectives and provides insights into the potential implications of the identified inhibitors for MLD therapy. However, it would be valuable to discuss the limitations of the computational approach employed, including assumptions and uncertainties associated with virtual screening, molecular dynamics simulations, and pharmacokinetic predictions.

Additionally, discussing the potential experimental validation of the identified inhibitors, such as in vitro enzymatic assays or cell-based assays, would strengthen the discussion and provide direction for future research.

The conclusion provides a concise summary of the study findings and emphasizes the potential of the identified phytoconstituents as CST inhibitors for MLD therapy. It might be beneficial to include recommendations for future research directions, such as experimental validation studies or further optimization of the identified inhibitors.

Ensure the manuscript is free of typographical and grammatical errors. Proofreading and editing will enhance readability.

Overall, the paper presents a rigorous computational study with well-defined methodologies and comprehensive analyses. The findings contribute to the understanding of CST inhibition for MLD therapy and offer potential drug candidates for further investigation.

Addressing minor points such as providing additional context, discussing limitations, and suggesting future research directions would enhance the clarity and impact of the paper. I recommend accepting the manuscript after these minor revisions are made.

Reviewer #3: The present paper describes screening of phytoconstituents from Bacopa monnieri (L.) Pennell and Mucuna

pruriens (L.) DC. to identify potential inhibitors against Cerebroside Sulfotransferase. The research is well documented and presented through docking analysis and they have identified IMPHY009537 from Bacopa monnieri IMPHY004141 from Mucuna pruriens as the second-best performing inhibitor against CST. The studies are important for development of oral drug for inhibiting CST and to inhibit the metachromatic leukodystrophy disease.

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Reviewer #1: No

Reviewer #2: Yes: Sutanu Nandi

Reviewer #3: Yes: Dr Dinesh Pandey

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Attachments

Attachment

Submitted filename: Review report on Screening of phytoconstituents from Bacopa.pdf

Screening of phytoconstituents from Bacopa monnieri (L.) Pennell and Mucuna pruriens (L.) DC. to identify potential inhibitors against Cerebroside Sulfotransferase.

PONE-D-24-19810R1

Dear Dr. SINGH,

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,

Rajesh Kumar Pathak, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have satisfactorily addressed all the comments and concerns raised by the reviewers. Therefore, I recommend the manuscript for publication.

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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: N/A

Reviewer #2: N/A

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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: Yes

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: Yes

Reviewer #2: 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)

Reviewer #2: The authors have adequately addressed all of my comments, such as providing additional context, discussing limitations, and suggesting future research directions. These changes enhance the clarity and impact of the paper. I recommend accepting the manuscript.

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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: Dev Bukhsh Singh

Reviewer #2: No

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