X-ray lightsource at DESY identifies promising candidates for COVID drugs

Electron density map of the most antiviral active ingredient calpeptin (yellow) binding at the main protease.

Electron density map of the most antiviral active ingredient calpeptin (yellow) binding at the main protease. © DESY/Sebastian Günther

At DESY's high-brilliance X-ray light source PETRA III, a team from more than 30 research institutions has identified several candidates for active substances against the coronavirus SARS-CoV-2. They bind to an important protein of the virus and could thus be the basis for a drug against Covid-19. The MX team from HZB examined part of the measurement data with special analysis algorithms in order to identify suitable active substances. The study has now been published in the renowned journal Science.

In a so-called X-ray screening, the researchers, under the leadership of DESY, tested almost 6000 known active substances that already exist for the treatment of other diseases in a short amount of time. After measuring about 7000 samples, the team was able to identify a total of 37 substances that bind to the main protease (Mpro) of the SARS-CoV-2 virus, as the scientists report online today in the journal Science. Seven of these substances inhibit the activity of the protein and thus slow down the multiplication of the virus. Two of them do this so promisingly that they are currently under further investigation in preclinical studies. This drug screening – probably the largest of its kind – also revealed a new binding site on the main protease of the virus to which drugs can couple.

“The active substances Calpeptin and Pelitinib clearly showed the highest antivirality with good cell compatibility. Our cooperation partners have therefore already started preclinical investigations with these two substances,” explains DESY researcher Sebastian Günther, first author of the Science publication.

In addition to DESY scientists, researchers from the Universities of Hamburg and Lübeck, the Bernhard Nocht Institute for Tropical Medicine, the Fraunhofer Institute for Translational Medicine and Pharmacology, the Heinrich Pette Institute, the European XFEL, the European Molecular Biology Laboratory EMBL, the Max Planck Society, the Helmholtz-Zentrum Berlin and other institutions are involved in the work.

Note: This is a shortened version of the full text of the press release published at DESY Website.