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

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            Abstract

            More 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 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
            11 March 2022
            Affiliations
            [1 ] Department of Obstetrics and Gynecology, Medicina Plus Medical Center, Istanbul, Turkey
            Author notes
            Author information
            https://orcid.org/0000-0002-5794-688X
            Article
            10.14293/S2199-1006.1.SOR-.PP5U8L4.v1
            144fed57-ada0-4d1b-a82c-9b2e1c0f102a

            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 .

            History
            : 11 March 2022

            The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
            Medicine,Life sciences
            COVID-19, SARS-CoV-2, Viral tropism, Spike protein, ACE2, STRA6, GPCR, GnRHR, Omicron, Multi-receptor mechanism, retinoid signaling

            Comments

            You are the shameless, dishonest, dishonest man Mahmod. Don't you have any shame? I have correspondence and evidence that I wrote this article and sent it to you via WhatsApp. I also shared them with the editor.
            We have been working with Mahmoud Elkazzaz for about 4-5 months. I wrote this whole article. I sent it to him to include himself and his other friends. But he deleted my name and preprinted it on scienceopen as if it 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.
            This is a very obvious theft of ideas and labor. He published the same article at the address ''https://osf.io/a6r3g/'' by changing the main title and sub-titles. I also wrote the final versions of the STRA6, GPCR, 9-Cis retinoic acid study, and LZTFL1 papers.

            Mahmut Elkazzaz is a thief. He copies the works of other researchers and presents them as his own. This bastard has no place in science.

            I respectfully report to the scientific community.

            https://osf.io/n6ybm/

            https://www.scienceopen.com/document?vid=708a6008-3360-4cdf-ab53-5dbba7abfcae

             

             

            2022-08-19 08:05 UTC
            +1

            https://www.scienceopen.com/hosted-document?doi=10.14293/S2199-1006.1.SOR-.PP8LWHL.v1All people should know your false truth, you shameless traitor deceiver. Publication dates do not lie, you traitor Turk. Damn you. You have brought shame to Turkey. They must execute you and kill you. This discovery is the basis of our clinical study.

            https://www.medrxiv.org/content/10.1101/2022.03.05.22271959v1

             

            2022-06-10 21:49 UTC
            +1

            Are you crazy this is our discovery 

            You stole our work

            https://loop.frontiersin.org/people/1149287/overview

            Published 2021

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

            Elkazzaz, Mahmoud Ramadan, Haydara, Tamer, Abo-Amer, Yousry Esam-Eldin, Sahyon, Heba, Shamkh, Israa, Magd, Mohammed F. Abo El, Cen, Osman, Sarohan, Aziz Rodan, Ahmed, Amr.EuropePMC; 2021.Preprint em Inglês | EuropePMC | ID: ppcovidwho-296649

             

            And it was published in February, before you publish it, you are a thief, a traitor and a madman. Shame on you. Shame on you, which gave birth to a traitor and fake like you, you bastard. Do you think you will deceive people, you crazy old man?

             

            Our publishing on February

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

             

             

            The Theif---------- Aziz   publishing on march  https://www.scienceopen.com/hosted-document?doi=10.14293/S2199-1006.1.SOR-.PPXLYQW.v1

             

             

            All people should know your false truth, you shameless traitor deceiver. Publication dates do not lie, you traitor Turk. Damn you. You have brought shame to Turkey. They must execute you and kill you. This discovery is the basis of our clinical study.

            https://www.medrxiv.org/content/10.1101/2022.03.05.22271959v1

            2022-06-10 21:45 UTC
            +1
            One person recommends this

            Are you crazy this is our discovery 

             

            You stole our work

             

            https://loop.frontiersin.org/people/1149287/overview

             

            Published 2021

             

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

             

            Elkazzaz, Mahmoud Ramadan, Haydara, Tamer, Abo-Amer, Yousry Esam-Eldin, Sahyon, Heba, Shamkh, Israa, Magd, Mohammed F. Abo El, Cen, Osman, Sarohan, Aziz Rodan, Ahmed, Amr.EuropePMC; 2021.Preprint em Inglês | EuropePMC | ID: ppcovidwho-296649

             

             

             

            And it was published in February, before you publish it, you are a thief, a traitor and a madman. Shame on you. Shame on you, which gave birth to a traitor and fake like you, you bastard. Do you think you will deceive people, you crazy old man?

             

             

            Our publishing on February

             

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

             

             

             

             

             

            The Theif---------- Aziz publishing on march https://www.scienceopen.com/hosted-document?doi=10.14293/S2199-1006.1.SOR-.PPXLYQW.v1

             

             

             

             

             

            All people should know your false truth, you shameless traitor deceiver. Publication dates do not lie, you traitor Turk. Damn you. You have brought shame to Turkey. They must execute you and kill you. This discovery is the basis of our clinical study.

             

            https://www.medrxiv.org/content/10.1101/2022.03.05.22271959v1

            2022-06-10 21:42 UTC
            +1
            One person recommends this

            Are you crazy this is our discovery 

            You stole our work

            https://loop.frontiersin.org/people/1149287/overview

            Published 2021

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

            Elkazzaz, Mahmoud Ramadan, Haydara, Tamer, Abo-Amer, Yousry Esam-Eldin, Sahyon, Heba, Shamkh, Israa, Magd, Mohammed F. Abo El, Cen, Osman, Sarohan, Aziz Rodan, Ahmed, Amr.EuropePMC; 2021.Preprint em Inglês | EuropePMC | ID: ppcovidwho-296649

             

            And it was published in February, before you publish it, you are a thief, a traitor and a madman. Shame on you. Shame on you, which gave birth to a traitor and fake like you, you bastard. Do you think you will deceive people, you crazy old man?

             

            Our publishing on February

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

             

             

            The Theif---------- Aziz   publishing on march  https://www.scienceopen.com/hosted-document?doi=10.14293/S2199-1006.1.SOR-.PPXLYQW.v1

             

             

            All people should know your false truth, you shameless traitor deceiver. Publication dates do not lie, you traitor Turk. Damn you. You have brought shame to Turkey. They must execute you and kill you. This discovery is the basis of our clinical study.

            https://www.medrxiv.org/content/10.1101/2022.03.05.22271959v1

             

            2022-06-10 21:27 UTC
            +1
            One person recommends this

            Are you crazy this is our discovery 

            You stole our work

            https://loop.frontiersin.org/people/1149287/overview

            Published 2021

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

            Elkazzaz, Mahmoud Ramadan, Haydara, Tamer, Abo-Amer, Yousry Esam-Eldin, Sahyon, Heba, Shamkh, Israa, Magd, Mohammed F. Abo El, Cen, Osman, Sarohan, Aziz Rodan, Ahmed, Amr.EuropePMC; 2021.Preprint em Inglês | EuropePMC | ID: ppcovidwho-296649

             

            And it was published in February, before you publish it, you are a thief, a traitor and a madman. Shame on you. Shame on you, which gave birth to a traitor and fake like you, you bastard. Do you think you will deceive people, you crazy old man?

             

            Our publishing on February

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

             

             

            The Theif---------- Aziz   publishing on march  https://www.scienceopen.com/hosted-document?doi=10.14293/S2199-1006.1.SOR-.PPXLYQW.v1

             

             

            All people should know your false truth, you shameless traitor deceiver. Publication dates do not lie, you traitor Turk. Damn you. You have brought shame to Turkey. They must execute you and kill you. This discovery is the basis of our clinical study.

            https://www.medrxiv.org/content/10.1101/2022.03.05.22271959v1

            2022-06-10 21:43 UTC

            Are you crazy this is our discovery 

            You stole our work

            https://loop.frontiersin.org/people/1149287/overview

            Published 2021

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

            Elkazzaz, Mahmoud Ramadan, Haydara, Tamer, Abo-Amer, Yousry Esam-Eldin, Sahyon, Heba, Shamkh, Israa, Magd, Mohammed F. Abo El, Cen, Osman, Sarohan, Aziz Rodan, Ahmed, Amr.EuropePMC; 2021.Preprint em Inglês | EuropePMC | ID: ppcovidwho-296649

             

            And it was published in February, before you publish it, you are a thief, a traitor and a madman. Shame on you. Shame on you, which gave birth to a traitor and fake like you, you bastard. Do you think you will deceive people, you crazy old man?

             

            Our publishing on February

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

             

             

            The Theif---------- Aziz   publishing on march  https://www.scienceopen.com/hosted-document?doi=10.14293/S2199-1006.1.SOR-.PPXLYQW.v1

             

             

            All people should know your false truth, you shameless traitor deceiver. Publication dates do not lie, you traitor Turk. Damn you. You have brought shame to Turkey. They must execute you and kill you. This discovery is the basis of our clinical study.

            https://www.medrxiv.org/content/10.1101/2022.03.05.22271959v1

            2022-06-10 21:42 UTC

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