SFB1328 Researchers, headed by project A18, have succeeded in developing novel active substances against SARS-CoV-2. This work has just been published in Nature Communications.
Coronaviruses such as SARS-CoV-2 can replicate undetected in infected cells for long periods by specifically disabling the cell’s natural antiviral defence mechanisms. The so-called Mac1 macrodomain plays a key role in this process – a viral enzyme that removes an important cellular marker (ADP-ribose) from proteins, thereby suppressing the cell’s immune defences. Through a detailed analysis of the binding between Mac1 and ADP-ribose, the researchers identified key interactions and, on this basis, developed new, highly effective inhibitors. In cell cultures infected with SARS-CoV-2, the active substances were shown to effectively suppress the virus’s replication. As numerous other viruses also possess similar macrodomains, the findings could pave the way for the development of a new class of antiviral drugs that are effective against several different viruses.
The work was carried out as part of an international collaboration between the UKE, the University of Hamburg, the EMBL, the University of Oxford (UK) and the CNRS in Marseille (France), and forms part of the Collaborative Research Centre ‘Adenine nucleotides in immunity and inflammation’ (SFB1328), led by the UKE.