Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Functional pangenome analysis suggests inhibition of the protein E as a readily available therapy for COVID-2019

Intikhab alam, Allan Kamau, Maxat Kulmanov, Stefan T. Arold, View ORCID ProfileArnab Pain, Takashi Gojobori, Carlos M. Duarte
doi: https://doi.org/10.1101/2020.02.17.952895
Intikhab alam
1King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), Thuwal, 23955-6900, Saudi Arabia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Intikhab.Alam@kaust.edu.sa Carlos.Duarte@kaust.edu.sa
Allan Kamau
1King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), Thuwal, 23955-6900, Saudi Arabia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maxat Kulmanov
1King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), Thuwal, 23955-6900, Saudi Arabia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stefan T. Arold
1King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), Thuwal, 23955-6900, Saudi Arabia
2Centre de Biochimie Structurale, CNRS, INSERM, Université de Montpellier, 34090 Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arnab Pain
3Biological and Environmental Science and Engineering (BESE), Thuwal, 23955-6900, Saudi Arabia
4Research Center for Zoonosis Control, Hokkaido University, Sapporo, 001-0020 Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Arnab Pain
Takashi Gojobori
1King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), Thuwal, 23955-6900, Saudi Arabia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carlos M. Duarte
1King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), Thuwal, 23955-6900, Saudi Arabia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Intikhab.Alam@kaust.edu.sa Carlos.Duarte@kaust.edu.sa
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Data/Code
  • Preview PDF
Loading

Abstract

The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells1. The S proteins from SARS-CoV-1 and SARS-CoV-2 are similar2, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-CoV-1–specific neutralizing antibodies to inhibit SARS-CoV-23. Here we used comparative pangenomic analysis of all sequenced Betacoronaviruses to reveal that, among all core gene clusters present in these viruses, the envelope protein E shows a variant shared by SARS and SARS-Cov2 with two completely-conserved key functional features, an ion-channel and a PDZ-binding Motif (PBM). These features trigger a cytokine storm that activates the inflammasome, leading to increased edema in lungs causing the acute respiratory distress syndrome (ARDS)4-6, the leading cause of death in SARS-CoV-1 and SARS-CoV-2 infection7,8. However, three drugs approved for human use may inhibit SARS-CoV-1 and SARS-CoV-2 Protein E, either acting upon the ion channel (Amantadine and Hexamethylene amiloride9,10) or the PBM (SB2035805), thereby potentially increasing the survival of the host, as already demonstrated for SARS-CoV-1in animal models. Hence, blocking the SARS protein E inhibits development of ARDS in vivo. Given that our results demonstrate that the protein E subcluster for the SARS clade is quasi-identical for the key functional regions of SARS-CoV-1 and SARS-CoV-2, we conclude that use of approved drugs shown to act as SARS E protein inhibitors can help prevent further casualties from COVID-2019 while vaccines and other preventive measures are being developed.

Footnotes

  • http://pangenomedb.cbrc.kaust.edu.sa

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted March 06, 2020.
Download PDF
Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Functional pangenome analysis suggests inhibition of the protein E as a readily available therapy for COVID-2019
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Functional pangenome analysis suggests inhibition of the protein E as a readily available therapy for COVID-2019
Intikhab alam, Allan Kamau, Maxat Kulmanov, Stefan T. Arold, Arnab Pain, Takashi Gojobori, Carlos M. Duarte
bioRxiv 2020.02.17.952895; doi: https://doi.org/10.1101/2020.02.17.952895
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Functional pangenome analysis suggests inhibition of the protein E as a readily available therapy for COVID-2019
Intikhab alam, Allan Kamau, Maxat Kulmanov, Stefan T. Arold, Arnab Pain, Takashi Gojobori, Carlos M. Duarte
bioRxiv 2020.02.17.952895; doi: https://doi.org/10.1101/2020.02.17.952895

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4235)
  • Biochemistry (9136)
  • Bioengineering (6784)
  • Bioinformatics (24001)
  • Biophysics (12129)
  • Cancer Biology (9534)
  • Cell Biology (13778)
  • Clinical Trials (138)
  • Developmental Biology (7636)
  • Ecology (11702)
  • Epidemiology (2066)
  • Evolutionary Biology (15513)
  • Genetics (10644)
  • Genomics (14326)
  • Immunology (9483)
  • Microbiology (22840)
  • Molecular Biology (9090)
  • Neuroscience (48995)
  • Paleontology (355)
  • Pathology (1482)
  • Pharmacology and Toxicology (2570)
  • Physiology (3846)
  • Plant Biology (8331)
  • Scientific Communication and Education (1471)
  • Synthetic Biology (2296)
  • Systems Biology (6192)
  • Zoology (1301)