Molecular Docking and ADME-TOX Profiling of Moringa oleifera Constituents against SARS-CoV-2

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors implemented a series of in silico studies to identify natural products as potential molecular targets of SARS-CoV-2. In this reviewer's opinion, the authors should address several important points to improve the research study and the manuscript. Hereunder are the main points:

MAJOR

1. Abstract: emphasize the novelty of this work. Several (>100) computational studies have been performed to identify potential inhibitors of SARS-CoV-2 targets.

2. Introduction: Acknowledge several review papers discussing the virtual screening of natural products Vs. COVID-19 targets. Comment on those studies with experimental validation.

3. Introduction: See and discuss the central insights of the review paper: A critical overview of computational approaches employed for COVID-19 drug discovery | https://doi.org/10.1039/D0CS01065K

4. Introduction: Clarify to the reader the difference between bioinformatics, chemoinformatics, and molecular modeling.

5. Methods: Revise the terminology. Why binders? More importantly, section 2.1 needs to provide details of how many compounds were studied, the curation protocol, and details of the geometry optimization.

6. Methods: Discuss the validation of the docking protocol. Also, justify the selection of the PDBs and discuss if such structures have been used in previous virtual screenings.

7. Results and conclusions: Have the natural products identified in this work as potential hits been previously identified in previous virtual screenings?

8. Consider the ligand efficiency to evaluate the potetial binders.

Author Response

First of all, we thank the reviewers for helpful comments and suggestions, which greatly improved the manuscript. The authors have taken into account all the reviewer comments and criticisms.

The authors implemented a series of in silico studies to identify natural products as potential molecular targets of SARS-CoV-2. In this reviewer's opinion, the authors should address several important points to improve the research study and the manuscript. Hereunder are the main points:

1. Abstract: emphasize the novelty of this work. Several (>100) computational studies have been performed to identify potential inhibitors of SARS-CoV-2 targets.

Dear reviewers, we have included in the abstract the novelty of this work that shows the antiviral potential of M. oleifera against Covid-19, testing with four essential targets in the process of viral replication, namely the mpro, spike, ACE2 and RBD proteins, not there are published works showing the anti-covid-19 action for this species against these four receptors.

2. Introduction: Acknowledge several review papers discussing the virtual screening of natural products Vs. COVID-19 targets. Comment on those studies with experimental validation.

Thanks for the observation. In the introduction, we acknowledge several review articles that discuss virtual screening of natural products against COVID-19 targets and also mention studies with experimental validation.

 

3. Introduction: See and discuss the central insights of the review paper: A critical overview of computational approaches employed for COVID-19 drug discovery | https://doi.org/10.1039/D0CS01065K

Thank you for this valuable suggestion. In the introduction, we referenced the central insights of the review article.

 

4. Introduction: Clarify to the reader the difference between bioinformatics, chemoinformatics, and molecular modeling.?

Dear reviewer, we have detailed in the introduction the main points covered in this paper.

 

5. Methods: Revise the terminology. Why binders? More importantly, section 2.1 needs to provide details of how many compounds were studied, the curation protocol, and details of the geometry optimization.

Thank you for your observations. In section 2.1, we provide details on the number of compounds studied, the curation protocol. Clarifying that the optimization of the molecules was not carried out, so that part that mentioned optimization was removed.

 

6. Methods: Discuss the validation of the docking protocol. Also, justify the selection of the PDBs and discuss if such structures have been used in previous virtual screenings.

We thank the reviewer for the suggestions. In the methods section, we discuss the validation of the docking protocol and justify the selection of PDBs, clarifying whether these structures have been used in previous virtual screenings.

 

7. Results and conclusions: Have the natural products identified in this work as potential hits been previously identified in previous virtual screenings?

Dear reviewer, in the results and conclusions section, we detail the research on the natural products identified as potential hits, including whether they were identified in previous virtual screenings.

 

8. Consider the ligand efficiency to evaluate the potetial binders.

We take ligand efficiency into account when evaluating potential ligands and incorporate this consideration into our analysis.

Reviewer 2 Report

Comments and Suggestions for Authors

In the manuscript ID: arm-2616671 entitled “Molecular docking and ADME-TOX profiling of Moringa oleifera constituents against SARS-CoV-2” the Authors describe in silico studies on the antiviral activity of 61 ligands using molecular docking procedure and ADME-TOX predictions.  I can recommend this manuscript for publication after minor revision. Some comments:

1. The molecular docking procedure could be described in more detail. How was the active site selected in the analyzed proteins? Was reference docking performed to indicate the correct selection of the method and the reliability of the results obtained?

2. Are ACE2 and ECA2 symbols for the same protein or are they symbols for two different proteins?

3. In the "Conclusion" section, there are no clear indications of the suitability of the tested compounds for therapeutic purposes resulting from the ADME-TOX analysis.

Author Response

First of all, we thank the reviewers for helpful comments and suggestions, which greatly improved the manuscript. The authors have taken into account all the reviewer comments and criticisms.

In the manuscript ID: arm-2616671 entitled “Molecular docking and ADME-TOX profiling of Moringa oleifera constituents against SARS-CoV-2” the Authors describe in silico studies on the antiviral activity of 61 ligands using molecular docking procedure and ADME-TOX predictions.  I can recommend this manuscript for publication after minor revision. Some comments:

 

1. The molecular docking procedure could be described in more detail. How was the active site selected in the analyzed proteins? Was reference docking performed to indicate the correct selection of the method and the reliability of the results obtained?

We appreciate your comments. We describe in more detail the molecular coupling procedure, including the selection of the active site in the analyzed proteins. We also performed reference docking to validate the method selection and the reliability of the results obtained.

 

2. Are ACE2 and ECA2 symbols for the same protein or are they symbols for two different proteins?

Dear reviewer, the symbols ACE2 and ACE2 represent the same protein. We replaced all ACE2 with ACE2 in the manuscript.

 

3. In the "Conclusion" section, there are no clear indications of the suitability of the tested compounds for therapeutic purposes resulting from the ADME-TOX analysis.

Dear reviewer, in the conclusion section we have added clear indications about the suitability of the tested compounds for therapeutic purposes based on the results of the ADME-TOX analysis.