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      Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19

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            Abstract

            BackgroundMore than two years have passed since the pandemic and despite all the efforts of researchers, the pathogenesis of COVID-19 has not yet been resolved. Multisystem involvement, neuroendocrine involvement, and pathophysiological changes caused by SARS-CoV-2 in peripheral organs have been shown in many studies. However, the molecular mechanism of these pathophysiological changes caused by COVID-19 has not been elucidated. The frequent mutations of SARS-CoV-2 and the change in the interaction of the virus with host cells have further complicated the pathogenetic mechanism in COVID-19. Unfortunately, the mechanism determined at the beginning of the pandemic and based on the single receptor tropism of ACE2 was insufficient to explain the pathogenesis of COVID-19. It is known that SARS-CoV-2 causes retinoid signaling defects and chemosensory receptor disorders and exerts its pathogenic effects through these mechanisms. Multisystem involvement and different clinical presentations in COVID-19 suggest that virus-host interaction develops through multiple receptors and signaling pathways. The previous mechanism described via ACE2, based on single-receptor tropism, was insufficient to elucidate the pathogenesis of COVID-19 due to the absence of ACE2 receptors in most of the affected organs. In addition, there is no satisfactory explanation for the mechanism by which ACE2-free organs are affected in COVID-19. In this regard, we think that ACE2 is not a true binding receptor for the SARS-CoV-2 spike protein. With our recent molecular docking studies, STRA6 and its GPCRs were identified as new binding receptors of the SARS-CoV-2 spike protein. These studies have brought a multi-receptor mechanism to the pathogenesis of COVID-19. The multi-receptor mechanism clearly illuminates the complex pathogenesis of retinoid signaling disorder, systemic organ involvement, neuroendocrine involvement, loss of smell and taste, and many other peripheral symptoms and signs, which are considered an enigma in the pathogenesis of COVID-19. Therefore, we suggest retinoid signaling defect as the main pathogenetic disorder in COVID-19 and STRA6 and GPCRs as the main binding receptors of SARS-CoV-2 spike protein. This new mechanism also clarifies the changing symptoms and findings in COVID-19 with each new variant. In addition, these studies have revealed new signaling pathways and drug targets for the treatment and prophylaxis of COVID-19.

            Content

            Author and article information

            Journal
            ScienceOpen Preprints
            ScienceOpen
            20 February 2022
            Affiliations
            [1 ] Department of Chemistry and Biochemistry, Faculty of Science, Damietta University, Egypt
            [2 ] Faculty of Medicine, Kafrelsheikh University, Egypt
            [3 ] Hepatology,Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital, Egypt
            [4 ] Chemo and Bioinformatics Lab, Bio Search Research Institution, BSRI. Giza , Egypt, Federal University of Alfenas, Brazil.
            [5 ] Zoology and Nematode department, Faculty of Agriculture , Al Azhar University, Cairo, Egypt
            [6 ] Director of tuberculosis program Ghubera, public health department ,First health cluster ,Ministry of health , Riyadh, Saudia Arabia.
            Author notes
            Article
            10.14293/S2199-1006.1.SOR-.PPXLYQW.v1
            d3aa51b5-d5c4-4bd6-89c1-35d38e723ae6

            This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .


            All data generated or analysed during this study are included in this published article (and its supplementary information files).
            Life sciences
            COVID-19,SARS-CoV-2,Spike protein,STRA6,GPCR,GnRHR,Anosmia,Multi-receptor mechanism,Omicron,CE2

            Comments

            https://osf.io/n6ybm/

            ''The article Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19'' is my own!

            Below I present new evidence that Mahmoud stole this article from me.
            There is no shame or honor in Mahmoud, but that will not deter me from seeking justice.
            Please look carefully
            1. The text uploaded to my site has been uploaded with the same name that I sent to it.
            2. The main font in which the text is written and the fonts in the part where Mahmoud adds his name are completely different. He did not pay attention to this detail when he deleted my name from the article and added his own.
            3. Below are the documents that the article was written by me and sent to you via WhatsApp for your name to be added. If you pay attention, the date the messages were written appears on the documents. You claimed that these were pre-arranged. The system assigns a new date to newly issued documents. Old dated messages can be deleted, there is no possibility to rearrange them. Will you learn that from me too?

            Note: The system (scienceopen) does not allow to uploading of pictures of correspondence. Evidence shared with scienceopen editors.

            Shame on you Mahmoud. I pity you, believe me. You ruined your honor. Whereas you claimed to be a great explorer. Was that your wits and honor, Mahmoud?
            I hope Scienceopen editors will do what is necessary soon. Otherwise, they will be prosecuted for being a tool for the theft of ideas and promoting the theft of ideas and works.

             

             

            2022-04-01 07:57 UTC
            +1

            Whoever is with Mahmud mentioned in Multireceptor and other related article is also a thief.  The person standing next to the thief is no different from the thief.  This is a serious ethical violation.  And you will all pay for it.

            2022-03-06 13:13 UTC
            +1
            One person recommends this

             

            Dear Dr. Stephanie Dawson

            Managing Director Scienceopen

            RE: Mahmoud Elkazzaz and Plagiarism

            Dear editor, Mahmoud Elkazzaz is committing a grave ethical violation. Do not use your magazine as a tool for this immorality and theft. Do not be complicit in this crime. I have reported this ethical violation to the Committee on Publication Ethics (COPE). Please end this injustice as soon as possible.
            There are phone records (in written form) that the article "Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19" was written by me and sent to Mahmoud Elkazaza via WhatsApp. It is also recorded on my personal computer when and for how long I wrote the article. The original text stays on my computer. Please remove this article that belongs to me but was stolen by a thief. Otherwise, you will be no different from a jeweler selling stolen goods. I present the details of the process to your attention below.

            We have been working with Egyptian researcher Mahmoud Elkazzaz for four or five months. I have rewritten and edited four of his previously preprinted articles in various online journals. Added my name to the new version of the two preprint presses. These were molecular docking studies. 

            I was writing and editing the articles. Then I was sending it to him via Whatsapp. He also sent it to magazines. I thought we didn't have any trust issues between us.

            However, he stole my last article titled “Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19”, which I wrote alone from point to comma. I sent this work to him via Whatsapp to add his own name and the names of his friends. However, he deleted my name and preprinted it for himself without touching the letter and the dot. Later, he added other names by editing. He preprinted the same article as another article by changing the main title and sub-headings on another site.

            I have been writing about the pathogenesis of COVID-19 and the mechanism of retinoid signaling for two years. I brought the first studies in this field to the literature: My studies are below;

            1. Sarohan AR. COVID-19: Endogenous Retinoic Acid Theory and Retinoic Acid Depletion Syndrome. Med Hypotheses. Nov 2020; 144:110250.

            https://pubmed.ncbi.nlm.nih.gov/33254555/

            2. Sarohan AR, Akelma H, Arac E, Aslan O. Retinol Depletion in Severe COVID-19. medRxiv, 2021.

            https://www.medrxiv.org/content/10.1101/2021.01.30.21250844v1

            3. Sarohan AR, Kızıl M, Inkaya AC, Mahmud S, Akram M, Cen O. A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder. Cell Signal. 2021 Aug 23:110121.

            (https://pubmed.ncbi.nlm.nih.gov/34438017/?s=09 )

            4. Sarohan AR. New Strategies for COVID-19 Vaccination and Adjuvant Prophylaxis. Journal of Vaccines & Vaccination 12 (2), 1000451

            https://www.longdom.org/abstract/new-strategies-for-covid19-vaccination-and-adjuvant-prophylaxis-64845.html

            5. Sarohan AR. Systemic Organ Involvement and Retinoid Signaling Disorder in COVID-19. Immunogenetics Open Access 6 (3), 1000141

            https://www.longdom.org/open-access/systemic-organ-involvement-and-retinoid-signaling-disorder-in-covid19.pdf

             

            Below are the sites where Mahmoud Elkazzaz preprinted my article for himself:

            1.https://www.scienceopen.com/hosted-document?doi=10.14293/S2199-1006.1.SOR-.PPXLYQW.v1

            (Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19)

            2. https://osf.io/a6r3g/

            (Crosstalk among COVID-19, STRA6, Retinol, and G protein-coupled receptor may explain the novel hypothesis of Retinol depletion and retinoid signaling disorder of COVID-19 pathogenesis).

            Mahmoud Elkazaaz was also working in this field. Six months ago, I discovered that he had extensively quoted (stolen) my article without reference in a Preprint article. He didn't refer to me.

            I also wrote a comment below. Reached me via LinkedIn. He offered to work together. We started working together. I rewrote and edited all preprint articles. He even added my name to two preprints and had it published as a new version.

            https://assets.researchsquare.com/files/rs-1079599/v4/0ec88d6c-9ea3-4c2a-968e-990d00c50170.pdf?c=1638906684

            https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/ppcovidwho-296649

            In this way, I started to think that there was no trust problem between us. I was writing the articles. He sent it to the magazines. Such a system was established over time. That's why I didn't hesitate to send the article I wrote from scratch by myself. I sent it as a Word file via Whatsapp. I even wrote two names from Turkey so that he could add his own name and the names of his friends, I wrote them to include them in the writing staff. At that time I had begun to write the 13-Cis Retinoic acid article.

            Two of El Kazzaz's molecular docking studies supported the retinoid signaling disorder theory I developed for COVID-19. By analyzing this, STRA6 and GPCR receptors developed the multi-receptor mechanism together with the ACE2 receptor to the pathogenesis of COVID-19, and I wrote a new article that discussed this together with the retinoid signaling disorder that I had developed before. This is how multi-receptor mechanism and retinoid signaling disorder occurred in the pathogenesis of COVID-19. I wrote this article from scratch from point to comma in the form of compilation analysis. And I sent it to Mahmud Elkzzaz to add his friends with his own name. Mahmud Elkazzaz did not contribute anything. He deleted my name from the article and reprinted it with his own name. In another place, he changed the main title and sub-titles and had a preprint made. In a review by the editors, it will be understood that the article exactly overlaps with the articles I wrote before in terms of writing style, style, shape, and emphasis, and it was written by me. There are correspondences stating that the article was written by me and sent to Mahmoud Elkazzaza for name addition. I am devastated that the article I wrote for days was lost to a thief.

            I need your support to prevent this theft of labor and science and to protect my rights. I need your support for the return of this study, which clearly explains the mechanism of multi-organ involvement, different clinical entities, and new variants, as well as the retinoid signaling mechanism in the pathogenesis of COVID-19. Change in clinical presentation in COVID-19.

            Mahmoud Elkazzaz, who does not recognize any moral rules and violates scientific ethical rules, has no place in the scientific community. I hope you believe in high ethical values. I request that the article titled "Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19", which I wrote from the beginning to the end and which Mahmoud Elkazzaz has made no contribution to, be removed from the scienceopen.com site. Please end this act, which is clear plagiarism and violation of ethical rules, as soon as possible.

            Dr. Aziz Rodan Sarohan M.D.

            2022-03-05 14:23 UTC
            +1

            You made other people a partner in your theft, mahmoud.  Those who do not want to be known as a thief for life in the academic world should withdraw their name from this article immediately.  This is my article and will remain so.

            2022-03-04 16:16 UTC
            +1

            Yy

            What a shame, man, are you crazy? This is my documented scientific discovery.This is a shame on you. You are doing something really disgraceful, as you are not young for such actions.

            Mahmoud Elkazzaz, Tamer Haydara, Yousry Esam-Eldin Abo-Amer et al. STRA6 (vitamin A receptor), as a Novel binding receptor of COVID-19 (A breakthrough), 13 September 2021, PREPRINT (Version 3) available at Research Square [https://doi.org/10.21203/rs.3.rs-892203/v3]

            https://www.researchsquare.com/article/rs-892203/v3

            Mahmoud Ramadan Elkazzaz, Amr Ahmed, Tamer Haydara et al. Discovering of GPCRSs and GnRHRs as SARS-CoV-2 binding receptors, the Scientific Breakthrough that could explain the observed Hypogonadism, Hypothyroidism, Anosmia, Retinol deficiency, Neurological and Menstrual disturbance among SARS-COV-2 patients., 14 December 2021, PREPRINT (Version 2) available at Research Square [https://doi.org/10.21203/rs.3.rs-1155356/v2]


            https://www.researchsquare.com/article/rs-1155356/v2

            Mahmoud Elkazzaz, Amr Kamel Khalil Ahmed and Israa Mohamed Shamkh et al. STRA6 (vitamin A receptor), as a Novel binding receptor of COVID-19 . ScienceOpen Preprints. DOI: 10.14293/S2199-1006.1.SOR-.PP8LWHL.v1

            Mahmoud Elkazzaz. Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19. ScienceOpen Preprints. DOI: 10.14293/S2199-1006.1.SOR-.PPXLYQW.v1


            https://www.scienceopen.com/hosted-document?doi=10.14293/S2199-1006.1.SOR-.PPXLYQW.v1

            2022-03-03 14:25 UTC
            +1
            Journal

            Title: ScienceOpen Preprints

            Publisher: ScienceOpen

            Publication date (Electronic preprint): 20 February 2022

            Affiliations

            [1 ] Department of Chemistry and Biochemistry, Faculty of Science, Damietta University, Egypt

            Author notes

             

            [* ]Email: mahmoudelkazzaz2051@ gmail.com .

            Article

            DOI: 10.14293/S2199-1006.1.SOR-.PPXLYQW.v1

            SO-VID: d3aa51b5-d5c4-4bd6-89c1-35d38e723ae6

            License:

            This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

            2022-03-03 14:22 UTC
            +1
            One person recommends this

            Dear editor
            scienceopen.com

            The article titled "Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19" posted on your website by Mahmud Elkazzaz belongs to me. I swear on my honor and honor, that I wrote this article from beginning to end by myself. Mahmoud Elkazzaz has not contributed one iota. While establishing the relationship between the multi-receptor mechanism and retinoid signaling in the pathogenesis of COVID-19, I mentioned STRA6 and GPCR receptors, which he had previously detected by molecular docking. For which I have appropriately cited references. I've been writing about the pathogenesis of COVID-19 and its relationship with retinoid signaling for two years already. If you examine this article, you will easily see its structural and logical relationship with my previous article.
            I sent this article to him on Whatsapp for Mahmoud Elkazzaz and his friends to add their names. I thought we didn't have any trust issues between us. But this naive and shameless thief deleted my name and sent the article to your site under his own name. Please do not give credit to this thief. This thief has no place in the scientific community either. As long as this article is live, it will give me pain. It pains me that my work, which I have worked for days, is standing there under the name of a thief. I want the article to be removed from the site as soon as possible.
            Kind regards.
            Dr.Aziz Rodan Sarohan M.D.

            2022-03-03 09:55 UTC
            +1
            One person recommends this

            We have been working with Mahmoud Elkazzaz for about 4-5 months. I wrote this article entirely. I sent it to him to include himself and his other friends. But as you can see, he deleted our names and sent them here as if they were his own work. The original text of the article is available on my computer. Readers will notice that this article logically overlaps with other articles I have written and found in the literature. It was a very obvious theft of ideas and labor. I request that this article be removed from the website as soon as possible. He published the same article on ''https://osf.io/a6r3g/'' by changing the main title and sub-titles. I also wrote the final versions of the STRA6 and GPCR papers. Mahmut Elkazzaz is a thief of ideas and labor.

            I respectfully report to the scientific community.

            Dr. Aziz Rodan Sarohan 

             

            NOT: The original article is as follows.

            Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19

             

            Aziz Rodan Sarohan 1*, Alpay Tuncar2, Abdurrahman Sarohan

             

            1. Department of Obstetrics and Gynecology, Medicina Plus Medical Center, İstanbul, Turkey

            2. Health Sciences University, Hamidiye Faculty of Medicine, Diskapi Yildirim Beyazit 

                  Training and Research Hospital, Department of Emergency Medicine

            3. Artuklu University, Mardin Training and Research Hospital, Department of Emergency Medicine

             * Corresponding author

            Department of Obstetrics and Gynecology, Medicina Plus Medical Center, 75. Yıl Mah., İstiklal Cad. 1305 Sk., No: 16 Sultangazi, İstanbul, Turkey 

            Email; azizrodan@gmail.com

             

            Link to my two related articles:

            https://www.sciencedirect.com/science/article/pii/S0306987720317898

            https://www.sciencedirect.com/science/article/pii/S0898656821002102

             

             

             

             

             

             

            2022-03-01 19:30 UTC
            +1
            One person recommends this

            Clown. You have no shame either. Didn't you say you were inspired by the articles I wrote earlier? You sent me the STRA6 article first, which I rewrote and edited. You added my name to the preprint version of this. Then you submitted the GPCR article, I wrote and edited it. You kept me busy, you didn't add my name to it. Then you submitted the 13-CIs retinoic acid study, which I rewrote and edited. After all this, I said that I would stone the studies with a compilation and analysis. I wrote the multi-receptor article from scratch to the dot myself. Here, I wrote about the relationship between STRA6 and GPCR receptors, which you found (perhaps stolen from elsewhere) by docking molecules, and retinoid signaling disorder. It is clear from the title of this article that I wrote it. Readers and editors will understand how similar the chosen words, accents, writing style, and style are to the articles I have written before. The articles are available in the WhatsApp records that I wrote and sent to you. I will share these with the editors.

            It pains me that a work that I wrote with great effort was stolen from me and published under the name of a thief. I will definitely make you pay for this. You are so immoral to submit an article to five journals at once. You have no manners, no manners, no shame, and no morals. You're breaking all the code of ethics. You have no place in the scientific community. You are shameless, cheeky, and a thief.

            2022-03-02 17:40 UTC

            Elkazzaz, M. (2022, February 23). Crosstalk among COVID-19, STRA6, Retinol, and G protein-coupled receptor may explain the novel hypothesis of Retinol depletion and retinoid signaling disorder of COVID-19 pathogenesis. https://doi.org/10.31219/osf.io/a6r3g

            2022-03-02 15:04 UTC

            What a shame, man, are you crazy? This is my documented scientific discovery.This is a shame on you. You are doing something really disgraceful, as you are not young for such actions.

            Mahmoud Elkazzaz, Tamer Haydara, Yousry Esam-Eldin Abo-Amer et al. STRA6 (vitamin A receptor), as a Novel binding receptor of COVID-19 (A breakthrough), 13 September 2021, PREPRINT (Version 3) available at Research Square [https://doi.org/10.21203/rs.3.rs-892203/v3]

            https://www.researchsquare.com/article/rs-892203/v3

            Mahmoud Ramadan Elkazzaz, Amr Ahmed, Tamer Haydara et al. Discovering of GPCRSs and GnRHRs as SARS-CoV-2 binding receptors, the Scientific Breakthrough that could explain the observed Hypogonadism, Hypothyroidism, Anosmia, Retinol deficiency, Neurological and Menstrual disturbance among SARS-COV-2 patients., 14 December 2021, PREPRINT (Version 2) available at Research Square [https://doi.org/10.21203/rs.3.rs-1155356/v2]


            https://www.researchsquare.com/article/rs-1155356/v2

            Mahmoud Elkazzaz, Amr Kamel Khalil Ahmed and Israa Mohamed Shamkh et al. STRA6 (vitamin A receptor), as a Novel binding receptor of COVID-19 . ScienceOpen Preprints. DOI: 10.14293/S2199-1006.1.SOR-.PP8LWHL.v1

            Mahmoud Elkazzaz. Multi-receptor mechanism and retinoid signaling disorder in the pathogenesis of COVID-19. ScienceOpen Preprints. DOI: 10.14293/S2199-1006.1.SOR-.PPXLYQW.v1


            https://www.scienceopen.com/hosted-document?doi=10.14293/S2199-1006.1.SOR-.PPXLYQW.v1

            2022-03-02 15:00 UTC

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