Repurposing drugs for a pan-coronavirus treatment
Drug targets common across three coronavirus strains could be used for
rapid treatment response against emerging coronavirus strains

Date:
October 15, 2020
Source:
European Molecular Biology Laboratory - European Bioinformatics
Institute
Summary:
A new study identifies drug targets common to all three
coronaviruses (SARS-CoV-2, SARS-CoV-1, and MERS-CoV) and potential
drugs that could be repurposed as COVID-19 treatments. Researchers
suggest that repurposed pan-coronavirus therapeutics may offer
a rapid treatment response against future emerging coronavirus
strains.



FULL STORY ==========================================================================
A large international consortium of almost 200 researchers from 14 leading institutions in six countries has studied three different coronaviruses
- - SARS-CoV-1, SARS-CoV-2, and MERS-CoV -- with the aim of finding vulnerabilities shared by these three pathogens. The research, published
in the journal Science, identifies important molecular mechanisms crucial
for all three coronaviruses, as well as potential drugs that could be repurposed as pan-coronavirus treatments.


==========================================================================
The consortium included researchers at EMBL's European Bioinformatics
Institute (EMBL-EBI), the Quantitative Biosciences Institute (QBI)
Coronavirus Research Group (QCRG) at University of California San
Francisco (UCSF), Gladstone Institutes, Institut Pasteur, Cluster of
Excellence CIBSS at the University of Freiburg, the Howard Hughes Medical Institute, and other collaborators including the biotechnology companies
Aetion and Synthego.

There are three known human respiratory syndromes associated with coronaviruses: severe acute respiratory syndrome (SARS), Middle
East respiratory syndrome (MERS), and coronavirus disease 2019
(COVID-19). These are caused by SARS-CoV-1, MERS-CoV, and SARS-CoV-2, respectively.

The scientists identified drug targets and repurposed therapeutics
that may have broad-spectrum activity across all three coronavirus
strains. Repurposed therapeutics with known safety profiles may offer
a rapid treatment response against emerging coronavirus strains in
the future.

Identifying coronavirus drug targets Building on their previous work
published in Nature and Cell, the scientists determined how viral and
human proteins interact, and where viral proteins are located within
host cells infected by different coronaviruses. They subsequently used
this data and functional genetic screening to identify host factors that prevent coronavirus propagation. The data analysed in this study will
be made freely accessible through the COVID-19 Data Portal.



========================================================================== "These analyses demonstrate how biological and molecular information
are translated into real-world implications for the treatment
of COVID-19 and other viral diseases," says Pedro Beltrao, Group
Leader at EMBL-EBI. "After more than a century of relatively harmless coronaviruses, in the last 20 years we've had three coronaviruses that
have been deadly. By looking across the species, we have the capability to predict pan-coronavirus therapeutics that may be effective in treating the current pandemic, which we believe will also offer promising therapeutics
for a future coronavirus as well." Another step to treat COVID-19 The researchers also performed real-world analysis on clinical data regarding COVID-19 patient outcomes. To do this, they identified molecules in human
cells that could be targeted with FDA-approved therapeutics and looked to
see what effect these drugs had on COVID-19 patients in the clinic. This analysis involved over 740,000 patients in the United States with known SARS-CoV- 2 infection.

The data and analysis carried out in this study demonstrate how molecular information can be translated into real-world implications for the
treatment of COVID-19. This study also showcases a collaborative approach
that can be applied to study other infectious agents in the future.

"This far-reaching international study elucidates for the first time commonalities and, importantly, vulnerabilities, across coronaviruses, including our current challenge with the COVID-19 pandemic," says
Nevan Krogan, Director of QBI and Senior Investigator at Gladstone
Institutes. "In unique and rapid fashion, we were able to bridge
biological and functional insights with clinical outcomes, providing an exemplary model of a differentiated way to conduct research into any
disease, rapidly identify promising treatments and advance knowledge
in the fields of both science and medicine. This body of work was only
made possible through the collaborative efforts of senior scientific
thought leaders and the teams of next-generation researchers at premier institutions across the globe." Funding This work was funded by grants
from the National Institute of Mental Health and the National Institute
of Allergy and Infectious Diseases, both part of the National Institutes
of Health; the Defense Advanced Research Projects Agency; the Center
for Research for Influenza Pathogenesis; the Centers of Excellence for Influenza Research and Surveillance of the National Institute of Allergy
and Infectious Diseases; the Centers of Excellence for Integrative
Biology of Emerging Infectious Diseases of the Agence Nationale de la
Recherche (France); F. Hoffmann-LaRoche AG; Vir Biotechnology, Centre
for Integrative Biological Signalling Studies (CIBSS), European Research Council (ERC) and the Ron Conway Family. A complete list of authors and
full funding information is available in the Science paper.


========================================================================== Story Source: Materials provided by European_Molecular_Biology_Laboratory_-_European
Bioinformatics_Institute. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. David E. Gordon et al. Comparative host-coronavirus protein
interaction
networks reveal pan-viral disease mechanisms. Science, Oct. 15,
2020; DOI: 10.1126/science.abe9403 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201015101822.htm

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