-->PONE-D-25-19182-->-->Identification of novel therapeutic inhibitors against E6 and E7 oncogenes of HPV-16 associated with cervical cancer-->-->PLOS ONE

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We look forward to receiving your revised manuscript.

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Prakash Palaniswamy, Ph.D

Academic Editor

PLOS ONE

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Additional Editor Comments:

Background and Significance

What role do the E6 and E7 oncogenes of HPV-16 play in the development of cervical cancer?

Why is HPV-16 considered one of the high-risk HPV types for cervical cancer?

How do the proteins expressed by E6 and E7 interfere with normal cell cycle regulation?

What are the current therapeutic approaches targeting HPV-associated cervical cancer?

Molecular Mechanisms

How does the E6 protein of HPV-16 contribute to the degradation of the tumor suppressor p53?

In what way does the E7 protein interact with the retinoblastoma (Rb) protein to promote oncogenesis?

What molecular pathways are dysregulated by E6 and E7 that lead to uncontrolled cell proliferation?

Therapeutic Inhibitors

What strategies have been explored to inhibit E6 and E7 oncogene activity in HPV-16 infected cells?

What are the advantages and challenges of targeting viral oncogenes directly versus downstream signaling pathways?

What types of molecules (small molecules, peptides, RNAi, CRISPR-based tools, etc.) have shown promise in inhibiting E6/E7 function?

How do in silico methods (e.g., molecular docking, virtual screening) contribute to the identification of potential inhibitors?

What are some examples of novel therapeutic inhibitors discovered recently against HPV-16 E6 and E7?

Experimental and Clinical Evaluation

What in vitro and in vivo models are commonly used to test the efficacy of E6/E7 inhibitors?

What biomarkers are used to assess the effectiveness of therapeutic agents targeting HPV oncogenes?

What are the main challenges in translating E6/E7 inhibitors from the lab to clinical trials?

How do resistance mechanisms impact the long-term efficacy of these inhibitors?

Broader Implications and Future Directions

How might combination therapies improve treatment outcomes for cervical cancer patients with HPV-16?

What role could therapeutic vaccines play in conjunction with E6/E7 inhibitors?

How could advances in delivery systems enhance the targeting of HPV oncogenes in cervical cancer?

What future research directions are critical for advancing the development of E6 and E7 inhibitors?

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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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Reviewer #1: Yes

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Reviewer #1: 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 is generally well-written, with a logical flow from introduction to conclusion.

The discussion could better integrate the biological relevance of E6 and E7 inhibition—how this translates to restoration of p53/Rb pathways, and what downstream effects are expected in cervical cancer cells.

Consider evaluating or discussing the off-target potential of the inhibitors, especially if the hits show broad-spectrum binding.

Some figures could be enhanced for clarity. Please ensure all visual elements are high resolution and properly labeled.

A few grammatical and typographical errors are present. A thorough proofreading or language editing will improve the manuscript’s professionalism.

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Reviewer #1: Yes:  Kannan Revathi

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Identification of novel therapeutic inhibitors against E6 and E7 oncogenes of HPV-16 associated with cervical cancer

PONE-D-25-19182R1

Dear Dr. Akter,

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.

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Kind regards,

Prakash Palaniswamy, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: