Drug Repurposing as strategy in the fight against COVID-19

Fraunhofer ITMP is applying Drug Repurposing strategies in various projects focusing on SARS-CoV-2. Here we report on the recent results.


After the recent successes in vaccine development, drug development against the COVID-19 disease is moving into focus. Therapeutics are urgently needed to provide treatment for unvaccinated populations or individuals who do not respond to vaccines. In addition, the disease treatment option offers a potential advantage if new variants of the virus emerge for which current vaccines are ineffective.


For drug development, knowledge of the mechanisms that lead to the development of a disease is a critical factor - the better we know the system, the easier it is to discover targets for therapy.

Since we currently do not fully understand how SARS-CoV-2 infects different tissues and organs and how this contributes to the development of the disease, we are using so-called "drug repurposing strategies" to screen known drug substances for their effect against COVID-19. These strategies cannot only identify effective substances for different  stages of the disease and verify their potential utility as combination therapeutics, but also contribute to a better understanding of the mechanisms of action of this disease. To this end, our screening and informatics infrastructure uses compound library-sets composed of marketed drugs, clinical and preclinical candidates, and small molecules regarded as safe in humans. Small molecules continue to represent the largest group of drugs used in almost all disease indications.

We have applied the repurposing strategy in the fight against COVID-19 both in the context of EU- and BMBF-funded initiatives, as well as internal projects within the "Fraunhofer vs. Corona" program. The first results have been publishe and, summarized in a movie (as of November 2020). A substance approved as a generic drug for osteoporosis is currently being tested in a clinical trial for COVID-19 patients with mild courses, for which a first evaluation is expected this summer. For more information on the study, please click  here.

Der Film zeigt unsere Strategie zur Repositionierung bereits bekannter Arzneimittel bei COVID-19 anhand unserer laufenden Forschungsprojekte. (Produziert von der Perspektive Media GmbH - November2020)

Publikations on our projects

A phenotypic repurposing screen for the identification of SARS-CoV-2 inhibitors

First screen with human cells infected with a Wuhan primary virus isolate.


Using the Fraunhofer ITMP Repurposing Collection, a set of approx. 5.600 clinical stage compounds, we identified 258 hits that inhibited SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2, by more than 75%. The most active molecules are currently under further investigation and may yield additional insights into SARS-CoV-2 mechanisms and potential therapeutic strategies.
All corresponding data sets have been disseminated and are publicly available (ChEMBL ID CHEMBL4303101) as our contribution to an open science community. Image data are deposited in The Image Data Resource (IDR) under the identifier idr0094.  

Identification of inhibitors of SARS-CoV-2 3CL-Pro enzymatic activity using a repurposing screen

Target confirmation of main protease.


SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. Within our repurposing program we confirmed previously reported inhibitors of 3CL-Pro and have identified 62 additional compounds with IC50 values below 1 μM. A subset of eight inhibitors showed anticytopathic effect in a Vero-E6 cell line. The X-ray crystal structure of the complex of one of the inhibitors and SARS-Cov-2 3CL-Pro was solved, showing covalent binding to the catalytic Cys145.

X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

Identification of 37 new repurposed drugs with approved direct 3D binding to SARS-CoV-2's main protease and reduce viral replication.


In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and six non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.103 authors mainly from science organizations in Hamburg contributed to this work. Among those, 5 scientists of Fraunhofer ITMP contributed scientific input, data interpretation and supply of the Fraunhofer ITMP Repurposing Collection to this X-ray crystallography screening effort. 

The COVID-19 Ontology

Ontology elementary for informatics approaches.


The COVID-19 pandemic has prompted an impressive, worldwide response by the academic community. In order to support text mining approaches as well as data description, linking and harmonization in the context of COVID-19, we have developed an ontology representing major novel coronavirus (SARS-CoV-2) entities. The ontology has a strong scope on chemical entities suited for drug repurposing, as this is a major target of ongoing COVID-19 therapeutic development. The ontology comprises 2.270 classes of concepts and 38.987 axioms (2622 logical axioms and 2434 declaration axioms). It depicts the roles of molecular and cellular entities in virus-host interactions and in the virus life cycle, as well as a wide spectrum of medical and epidemiological concepts linked to COVID-19. The performance of the ontology has been tested on Medline and the COVID-19 corpus provided by the Allen Institute. The COVID-19 Ontology is released under a Creative Commons 4.0 License and shared via https://github.com/covid-19-ontology/covid-19. The ontology is also deposited in BioPortal at https://bioportal.bioontology.org/ontologies/COVID-19.