Talk:WikiJournal Preprints/The Efficacy of Paxlovid against COVID-19 is the Result of the Tight Molecular Docking between Mpro and Antiviral Drugs (Nirmatrelvir and Ritonavir)
This article has been declined for publication by the WikiJournal Preprints.
It is archived here as a record. Discussion can be viewed below.
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QID: Q115704760
Suggested (provisional) preprint citation format:
Ali Adel Dawood. "The Efficacy of Paxlovid against COVID-19 is the Result of the Tight Molecular Docking between Mpro and Antiviral Drugs (Nirmatrelvir and Ritonavir)". WikiJournal Preprints. Wikidata Q115704760.
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This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction, provided the original author and source are credited.
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Christopher VanLang
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This article has been declined for publication by the WikiJournal Preprints.
It is archived here as a record. Discussion can be viewed below.
First peer review[edit source]
Review by Christopher VanLang , National Resilience
These assessment comments were submitted on , and refer to this previous version of the article
I had the chance to review the manuscript The Efficacy of Paxlovid against COVID-19 is the Results of the Tight Molecular Docking Between Mpro and Antiviral Drugs (Nirmatrelvir and Ritonavir).
To start, this manuscript seems to have already been submitted to Advances in Medical Science (https://doi.org/10.1016/j.advms.2022.10.001) on 13 July 2022 ahead of submission to the WikiJournal of Science on 22 July 2022. Regardless, the manuscript should be rejected based on the technical and scientific content. Some of the major concerns are:
- Overall, the construction of the scientific argument is messy. The opening hypotheses is generally unsupported and unwarranted. It would be more appropriate to dive directly into the importance of the viral proteases and the desire to understand the molecular mechanism of Mpro inhibitors and the impact of variants. The recommendation is to drastically simplify the hypothesis and conclusion. The major takeaway from these docking experiments seems to be that the P132H mutation of the omicron variant doesn’t have an effect on the docking. However if that was the hypothesis, then the docking experiments with 6Y2E and 6Y2E with P1232H should have been performed and the binding affinity compared. No data asides the visual evaluation were provided.
- The other conclusion that the complex with both nirmatrelvir and ritonavir was more stable than the single docked complex seems unsupported. It would be extremely helpful to have a figure of the nirmatrelvir+ritonavir Mpro complex showing the appearance of new interactions. Based on the ERRAT2 analysis, we should expect to see structural changes for the residues at 220; those residues aren’t depicted as interactions in Fig 1. Ideally, there should be an evaluation of the binding thermodynamics which isn’t present in this manuscript. Ultimately it may not matter since the generally accepted mechanism of action is that ritonavir is added as a booster to inhibit CYP3A4 and prolongs the distribution of nirmatrelvir.
- The references largely do not support the statements made in the manuscript nor are the original references where such hypotheses would have been made. For instance, the references discussing the mechanism of action of remdesivir through the inhibition of RdRp do not reference articles on RdRp but instead discuss Mpro. The discussions regarding the prior molecular docking research reference articles that don’t perform those experiments. These scattered unsupported references exist throughout the manuscript. In addition, references aren’t provided for the underlying methods used to perform the docking and simulation experiments.
Editorial comment[edit source]
Comments by Andrew Leung ,
These editorial comments were submitted on , and refer to this previous version of the article
Thank you to our reviewer who identified this manuscript as having submitted to another journal a week before submitting to us for publication consideration. As such, we are rejecting this submission due to violation of publication ethics and misled the editorial board when the author claimed that this work was not submitted simultaneously to another journal which would prohibit further publication.