Repurposing medication for a pan-coronavirus treatment

A large international consortium of almost 200 researchers from 14 leading institutions in six countries has examined three different coronaviruses – SARS-CoV-1, SARS-CoV-2 and MERS-CoV – with the aim of finding weak points in these three pathogens. The study, published in the journal Science, identifies key molecular mechanisms that are critical to all three coronaviruses, as well as potential drugs that could be used as pan-coronavirus treatments.

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

Three human respiratory syndromes are known to be associated with coronaviruses: Severe Acute Respiratory Syndrome (SARS), Middle Eastern Respiratory Syndrome (MERS), and Coronavirus Disease 2019 (COVID-19). These are caused by SARS-CoV-1, MERS-CoV or SARS-CoV-2.

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

Identification of 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 in host cells infected with various coronaviruses. They then used this data and functional genetic screening to identify host factors that prevent coronaviruses from multiplying. The data analyzed in this study are made freely accessible via the COVID-19 data portal.

“These analyzes show how biological and molecular information is translated into real effects on 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, we have had three deadly coronaviruses in the past 20 years. By looking at the species, we can predict pan-coronavirus therapeutics that may be effective in treating the current pandemic. We believe that they will offer promising therapeutics for a future coronavirus as well. ”

Another step in treating COVID-19

The researchers also performed a real-world analysis of 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 investigated the effects these drugs had on COVID-19 patients in the clinic. This analysis included over 740,000 patients in the US with known SARS-CoV-2 infection.

The data and analysis performed in this study show how molecular information can be translated into real-world implications for the treatment of COVID-19. This study also shows a collaborative approach that can be used to study other infectious agents in the future. “This far-reaching international study highlights for the first time similarities and especially weaknesses in coronaviruses, including our current challenge with the COVID-19 pandemic,” says Nevan Krogan, Director of the QBI and Senior Investigator at the Gladstone Institute. “We were able to combine biological and functional findings with clinical results in a unique and fast way and provide an exemplary model for a differentiated way of researching diseases, quickly identify promising treatments and expand knowledge in the scientific and medical field. This work has only been made possible by the collaboration of high-level scientific thought leaders and teams of next-generation researchers at leading institutions around the world. ”

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