Evidence map›Paper›PMID 36146578›Full record

ArticleVaccines2022

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

Mahmoud Elkazzaz, Amr Ahmed, Yousry Esam-Eldin Abo-Amer, Tamer Hydara, Abdullah Haikal, Dina N Abd El Razek, Wafa Ali Eltayb, Xiling Wang, Tomasz M Karpiński, Dalia Hamza and 2 more

Abstract read
In one paragraph

Article in Vaccines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Mahmoud ElkazzazDepartment of Chemistry and Biochemistry, Faculty of Science, Damietta University, Damietta 7952567, Egypt.
Amr AhmedDirector of Tuberculosis Ghubera Mobile Team, Public Health Department, First Health Cluster, Ministry of Health, Riyadh 966-11, Saudi Arabia.ORCID 0000-0003-3477-236X
Yousry Esam-Eldin Abo-AmerHepatology, Gastroenterology, and Infectious Diseases Department, Mahala Hepatology Teaching Hospital, El-Mahalla el-Kubra 31951, Egypt.
Tamer HydaraDepartment of Internal Medicine, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
Abdullah HaikalDepartment of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.ORCID 0000-0003-2548-3507
Dina N Abd El RazekDepartment of Biochemistry, Al Menoufia University, Shibin el Kom 32511, Egypt.ORCID 0000-0002-4476-8973
Wafa Ali EltaybBiotechnology Department, Faculty of Science and Technology, Shendi University, Shendi 11111, Nher Anile, Sudan.ORCID 0000-0002-3981-201X
Xiling WangChinese Academy of Sciences Key Laboratory of Biofuels and Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao 266000, China.
Tomasz M KarpińskiChair and Department of Medical Microbiology, Poznań University of Medical Sciences, Wieniawskiego 3, 61-712 Poznań, Poland.ORCID 0000-0001-6599-9204
Dalia HamzaDepartment of Zoonoses, Faculty of Veterinary Medicine, Cairo University, Giza 12613, Egypt.ORCID 0000-0001-7579-5432
Basit JabbarCentre of Excellence in Molecular Biology, University of the Punjab, Lahore 53700, Pakistan.ORCID 0000-0002-9577-1793
Israa M ShamkhChemo and Bioinformatics Lab, Bio Search Research Institution BSRI, Botany and Microbiology Department, Faculty of Science, Cairo University, Giza 12613, Egypt.ORCID 0000-0002-3260-4162

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

ACE2COVID-19GnRHRGPCRMD simulationmolecular dockingspike protein

Identifiers

PMID36146578
PMCPMC9504287

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.