Cargando…

In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19

Despite the intense research work since the beginning of the pandemic, the pathogenesis of COVID-19 is not yet clearly understood. The previous mechanism of COVID-19, based on ACE2 tropism and explained through a single receptor, is insufficient to explain the pathogenesis due to the absence of angi...

Descripción completa

Detalles Bibliográficos
Autores principales: Elkazzaz, Mahmoud, Ahmed, Amr, Abo-Amer, Yousry Esam-Eldin, Hydara, Tamer, Haikal, Abdullah, Razek, Dina N. Abd El, Eltayb, Wafa Ali, Wang, Xiling, Karpiński, Tomasz M., Hamza, Dalia, Jabbar, Basit, Shamkh, Israa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504287/
https://www.ncbi.nlm.nih.gov/pubmed/36146578
http://dx.doi.org/10.3390/vaccines10091500
_version_ 1784796177677418496
author Elkazzaz, Mahmoud
Ahmed, Amr
Abo-Amer, Yousry Esam-Eldin
Hydara, Tamer
Haikal, Abdullah
Razek, Dina N. Abd El
Eltayb, Wafa Ali
Wang, Xiling
Karpiński, Tomasz M.
Hamza, Dalia
Jabbar, Basit
Shamkh, Israa M.
author_facet Elkazzaz, Mahmoud
Ahmed, Amr
Abo-Amer, Yousry Esam-Eldin
Hydara, Tamer
Haikal, Abdullah
Razek, Dina N. Abd El
Eltayb, Wafa Ali
Wang, Xiling
Karpiński, Tomasz M.
Hamza, Dalia
Jabbar, Basit
Shamkh, Israa M.
author_sort Elkazzaz, Mahmoud
collection PubMed
description Despite the intense research work since the beginning of the pandemic, the pathogenesis of COVID-19 is not yet clearly understood. The previous mechanism of COVID-19, based on ACE2 tropism and explained through a single receptor, is insufficient to explain the pathogenesis due to the absence of angiotensin-converting enzyme 2 (ACE2) receptors in most of the affected organs. In the current study, we used the PatchDock server to run a molecular docking study of both the gonadotropin-releasing hormone receptor (GnRHR) and G-protein-coupled-receptor (GPCR) with the SARS-CoV-2 spike protein. Molecular Dynamics (MD) simulations were run to analyze the stability of the complexes using the GROMACS package. The docking results showed a high affinity between the spike protein with the GnRHR (−1424.9 kcal/mol) and GPCR (−1451.8 kcal/mol). The results of the MD simulations revealed the significant stability of the spike protein with the GnRHR and GPCR up to 100 ns. The SARS-CoV-2 spike protein had strong binding interactions with the GPCRs and GnRHRs, which are highly expressed in the brain, endocrine organs, and olfactory neurons. This study paves the way towards understanding the complex mechanism of neuroendocrine involvement and peripheral organ involvement, may explain the changing symptoms in patients due to new variants, and may lead to the discovery of new drug targets for COVID-19. In vitro studies involving genetic engineering or gene knockdown of the GPCRs and GnRHRs are needed to further investigate the role of these receptors in COVID-19 pathogenesis.
format Online
Article
Text
id pubmed-9504287
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-95042872022-09-24 In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19 Elkazzaz, Mahmoud Ahmed, Amr Abo-Amer, Yousry Esam-Eldin Hydara, Tamer Haikal, Abdullah Razek, Dina N. Abd El Eltayb, Wafa Ali Wang, Xiling Karpiński, Tomasz M. Hamza, Dalia Jabbar, Basit Shamkh, Israa M. Vaccines (Basel) Article Despite the intense research work since the beginning of the pandemic, the pathogenesis of COVID-19 is not yet clearly understood. The previous mechanism of COVID-19, based on ACE2 tropism and explained through a single receptor, is insufficient to explain the pathogenesis due to the absence of angiotensin-converting enzyme 2 (ACE2) receptors in most of the affected organs. In the current study, we used the PatchDock server to run a molecular docking study of both the gonadotropin-releasing hormone receptor (GnRHR) and G-protein-coupled-receptor (GPCR) with the SARS-CoV-2 spike protein. Molecular Dynamics (MD) simulations were run to analyze the stability of the complexes using the GROMACS package. The docking results showed a high affinity between the spike protein with the GnRHR (−1424.9 kcal/mol) and GPCR (−1451.8 kcal/mol). The results of the MD simulations revealed the significant stability of the spike protein with the GnRHR and GPCR up to 100 ns. The SARS-CoV-2 spike protein had strong binding interactions with the GPCRs and GnRHRs, which are highly expressed in the brain, endocrine organs, and olfactory neurons. This study paves the way towards understanding the complex mechanism of neuroendocrine involvement and peripheral organ involvement, may explain the changing symptoms in patients due to new variants, and may lead to the discovery of new drug targets for COVID-19. In vitro studies involving genetic engineering or gene knockdown of the GPCRs and GnRHRs are needed to further investigate the role of these receptors in COVID-19 pathogenesis. MDPI 2022-09-08 /pmc/articles/PMC9504287/ /pubmed/36146578 http://dx.doi.org/10.3390/vaccines10091500 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Elkazzaz, Mahmoud
Ahmed, Amr
Abo-Amer, Yousry Esam-Eldin
Hydara, Tamer
Haikal, Abdullah
Razek, Dina N. Abd El
Eltayb, Wafa Ali
Wang, Xiling
Karpiński, Tomasz M.
Hamza, Dalia
Jabbar, Basit
Shamkh, Israa M.
In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19
title In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19
title_full In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19
title_fullStr In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19
title_full_unstemmed In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19
title_short In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19
title_sort in silico discovery of gpcrs and gnrhrs as novel binding receptors of sars-cov-2 spike protein could explain neuroendocrine disorders in covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504287/
https://www.ncbi.nlm.nih.gov/pubmed/36146578
http://dx.doi.org/10.3390/vaccines10091500
work_keys_str_mv AT elkazzazmahmoud insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT ahmedamr insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT aboameryousryesameldin insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT hydaratamer insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT haikalabdullah insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT razekdinanabdel insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT eltaybwafaali insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT wangxiling insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT karpinskitomaszm insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT hamzadalia insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT jabbarbasit insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19
AT shamkhisraam insilicodiscoveryofgpcrsandgnrhrsasnovelbindingreceptorsofsarscov2spikeproteincouldexplainneuroendocrinedisordersincovid19