PONE-D-24-02007Investigation of Biometabolites and Novel Antimicrobial Peptides Derived from Promising Source Cordyceps militaris and Effect of Non-Small Cell Lung Cancer Genes ComputationallyPLOS ONE

Dear Dr. Ahmed,

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Jameel Al-Obaidi

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PLOS ONE

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Additional Editor Comments:

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ACADEMIC EDITOR:

Dear Author

I am writing to inform you about the decision regarding your manuscript titled "Investigation of Biometabolites and Novel Antimicrobial Peptides Derived from Promising Source Cordyceps militaris and Effect of Non-Small Cell Lung Cancer Genes Computationally," which has been under review.

After a thorough evaluation and consideration of the respected reviewers' comments, I am pleased to inform you that can be accepted with minor corrections. We believe that your research provides significant contributions to the field, especially in understanding the potential of Cordyceps militaris against Non-Small Cell Lung Cancer genes.

The reviewers have provided feedback aimed at enhancing the clarity, accuracy, and impact of your manuscript. To proceed, we kindly request that you address the following minor corrections suggested by the reviewers (Attached)

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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: 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: The manuscript explores a novel and promising research direction by investigating biometabolites and antimicrobial peptides derived from Cordyceps militaris, a source with significant potential for therapeutic applications. The integration of computational analysis to explore the effects on non-small cell lung cancer genes adds depth and relevance to the study, contributing to the advancement of both biotechnology and biomedical research fields.

The paper demonstrates a comprehensive experimental approach to isolate, characterize, and evaluate biometabolites and antimicrobial peptides from Cordyceps militaris. The detailed methodologies provided offer transparency and reproducibility, laying a solid foundation for future investigations in this area. The computational analysis of the interactions between biometabolites/antimicrobial peptides and non-small cell lung cancer genes is a notable strength of the study. By employing computational modeling and bioinformatics tools, the paper expands our understanding of potential therapeutic mechanisms and provides insights into the molecular pathways involved. The results section is well-structured and effectively presents the findings of the study. The inclusion of tables, figures, and supplementary data enhances the clarity and visualization of the experimental outcomes, facilitating interpretation and comparison with existing literature.

The discussion section offers insightful interpretations of the experimental results and effectively contextualizes them within the broader scientific literature. The authors critically analyze the implications of their findings and propose intriguing avenues for future research, stimulating further inquiry and innovation in the field.

In summary, the manuscript represents a significant advancement in our understanding of Cordyceps militaris-derived biometabolites and antimicrobial peptides, as well as their potential impact on non-small cell lung cancer. The combination of experimental and computational approaches, coupled with clear presentation and thoughtful interpretation of results, positions the study as a valuable contribution to both basic and translational research efforts in biotechnology and cancer biology.

Reviewer #2: Dear author please refer to the comments in the manuscript attached.

Dear Author,

Good day,

I am hereby writing my feedback on the scientific paper entitled “Investigation of Biometabolites and Novel Antimicrobial Peptides Derived from Promising Source Cordyceps militaris and Effect of Non-Small Cell Lung Cancer Genes Computationally “.

The manuscript is of good value due to its important character, it treats a specific subject that is of high interest for public health.

The present manuscript approaches an interesting topic, that is, to analyze the potentials of biometabolites and to extract antimicrobial peptides and protein from the C. militaris..

Thereby I would like to inform you that the paper is qualified to publish in this scientific journal with some minor revision as shown in the comments in the attached manuscripts .

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Reviewer #1: Yes: Assistant Professor Dr. Rana I. Mahmood

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PlosOne-Manuscript,rev.docx

PONE-D-24-02007R1Investigation of Biometabolites and Novel Antimicrobial Peptides Derived from Promising Source Cordyceps militaris and Effect of Non-Small Cell Lung Cancer Genes ComputationallyPLOS ONE

Dear Dr. Ahmed,

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.

Please submit your revised manuscript by Sep 27 2024 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,

Afzal Basha Shaik, Ph.D

Academic Editor

PLOS ONE

Journal Requirements:

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:

The authors have revised the manuscript according to the comments provided by the reviewers. However, it still needs minor revisions as per the additional reviewers comments and my concerns. I recommend to enrich the introduction part by including the following contents and references.

1. Genomics and metabolomics have been extensively investigated for the discovery of new drugs particularly in the discovery of peptide-based drugs. Add few lines about the same and cite the below references

a. Jiang, M., Chen, S., Lu, X., Guo, H., Chen, S., Yin, X.,... Liu, L. (2023). Integrating Genomics and Metabolomics for the Targeted Discovery of New Cyclopeptides with Antifungal Activity from a Marine-Derived Fungus Beauveria felina. Journal of Agricultural and Food Chemistry, 71(25), 9782-9795. doi: 10.1021/acs.jafc.3c02415.

b. Kloosterman, A.M., Medema, M.H. and van Wezel, G.P., 2021. Omics-based strategies to discover novel classes of RiPP natural products. Current Opinion in Biotechnology, 69, pp.60-67.

c. Xu, T., Yan, X., Kang, A., Yang, L., Li, X., Tian, Y.,... Guo, Y. (2024). Development of Membrane-Targeting Fluorescent 2-Phenyl-1H-phenanthro[9,10-d]imidazole-Antimicrobial Peptide Mimic Conjugates against Methicillin-Resistant Staphylococcus aureus. Journal of Medicinal Chemistry, 67(11), 9302-9317. doi: https://doi.org/10.1021/acs.jmedchem.4c00436

d. He, B., Lang, J., Wang, B., Liu, X., Lu, Q., He, J.,... Yang, J. (2020). TOOme: A Novel Computational Framework to Infer Cancer Tissue-of-Origin by Integrating Both Gene Mutation and Expression. Frontiers in Bioengineering and Biotechnology, 8. doi: 10.3389/fbioe.2020.00394

e. Ali, A.M., Atmaj, J., Van Oosterwijk, N., Groves, M.R. and Dömling, A., 2019. Stapled peptides inhibitors: a new window for target drug discovery. Computational and structural biotechnology journal, 17, pp.263-281.

2. Some of the important works related to the therapeutic modalities in non-small cell lung cancer were not referred. These must be discussed and cited in the introduction.

a. Zhao, Y., Chen, S., Shen, F., Long, D., Yu, T., Wu, M.,... Lin, X. (2019). In vitro neutralization of autocrine IL‑10 affects Op18/stathmin signaling in non‑small cell lung cancer cells. Oncol Rep, 41(1), 501-511. doi: 10.3892/or.2018.6795

b. Chen, S., Zhao, Y., Shen, F., Long, D., Yu, T.,... Lin, X. (2019). Introduction of exogenous wild‑type p53 mediates the regulation of oncoprotein 18/stathmin signaling via nuclear factor‑κB in non‑small cell lung cancer NCI‑H1299 cells. Oncol Rep, 41(3), 2051-2059. doi: 10.3892/or.2019.6964

c. Dai, J., Ashrafizadeh, M., Aref, A. R., Sethi, G., & Ertas, Y. N. (2024). Peptide-functionalized, -assembled and -loaded nanoparticles in cancer therapy. Drug Discovery Today, 29(7), 103981. doi: https://doi.org/10.1016/j.drudis.2024.103981

d. Tan, T., Feng, Y., Wang, W., Wang, R., Yin, L., Zeng, Y.,... Xie, T. (2023). Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer. Cancer Nanotechnology, 14(1), 70. doi: https://doi.org/10.1186/s12645-023-00194-7

e. Lou, J., Zhao, L., Huang, Z., Chen, X., Xu, J., TAI, W. C.,... Xie, T. (2021). Ginkgetin derived from Ginkgo biloba leaves enhances the therapeutic effect of cisplatin via ferroptosis-mediated disruption of the Nrf2/HO-1 axis in EGFR wild-type non-small-cell lung cancer. Phytomedicine, 80, 153370. doi: https://doi.org/10.1016/j.phymed.2020.153370

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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

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

Reviewer #4: (No Response)

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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

Reviewer #3: Yes

Reviewer #4: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: 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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: 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

Reviewer #3: Yes

Reviewer #4: 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)

Reviewer #3: The topic to which the manuscript “ Investigation of Biometabolites and Novel Antimicrobial Peptides Derived from Promising Source Cordyceps militaris and Effect of Non-Small Cell Lung Cancer Genes Computationally” is devoted is relevant and of practical importance. Due to a wide range of bioactive compounds, C. militaris has significant potential for pharmacological use. The manuscript is of a modern scientific level, impresses with its instrumental level of execution and depth of research.This work definitely deserves to be published and the results highlighted.

However, there are a number of recommendations that would improve the introduction.

The article is devoted to the study of the impact of Cordyceps militaris of Non-Small Cell Lung Cancer Genes. However, the introduction does not contain any information about the already published studies of the effect of this mushroom on non-small cell lung cancer. This information should be added and I recommend pay attention to the following works:

Luo L, Ran R, Yao J, Zhang F, Xing M, Jin M, Wang L, Zhang T. Se-Enriched Cordyceps militaris Inhibits Cell Proliferation, Induces Cell Apoptosis, And Causes G2/M Phase Arrest In Human Non-Small Cell Lung Cancer Cells. Onco Targets Ther. 2019;12:8751-8763 https://doi.org/10.2147/OTT.S217017

Jo E, Jang HJ, Shen L, Yang KE, Jang MS, Huh YH, Yoo HS, Park J, Jang IS, Park SJ. Cordyceps militaris Exerts Anticancer Effect on Non-Small Cell Lung Cancer by Inhibiting Hedgehog Signaling via Suppression of TCTN3. Integr Cancer Ther. 2020 Jan-Dec;19:1534735420923756. doi: 10.1177/1534735420923756.

Lu YY, Huang X, Luo ZC, et al. [Mechanism of Cordyceps militaris against non-small cell lung cancer: based on serum metabolomics]. Zhongguo Zhong yao za zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. 2022 Sep;47(18):5032-5039. DOI: 10.19540/j.cnki.cjcmm.20220613.702.

In my opinion, the information about the SDS-PAGE method (line 75-79) is unnecessary in the introduction. It is logical to provide this information in the discussion.

Line 112-113: The mushroom was taxonomically classified, identified and 113 confirmed from the University of Central Punjab, Lahore Pakistan.

Was the sample genetically identified? Was the data entered into the genebank? If yes, please provide the sample number.

Reviewer #4: (No Response)

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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: Yes: Dhafar N. Al-ugaili

Reviewer #3: No

Reviewer #4: No

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Attachments

Attachment

Submitted filename: PONE-D-24-02007_reviewer.pdf

Investigation of Biometabolites and Novel Antimicrobial Peptides Derived from Promising Source Cordyceps militaris and Effect of Non-Small Cell Lung Cancer Genes Computationally

PONE-D-24-02007R2

Dear Dr. Ahmed,

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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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,

Afzal Basha Shaik, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: