In the anti‑corona project ISE‑CoV‑2‑Screen Fraunhofer IGB is identifying therapeutic substances for the treatment of COVID‑19 patients. The focus is on molecules that have already been approved for another indication or are at least at an advanced stage of development (repurposing of drugs). In this project, Fraunhofer IGB collaborates with the Fraunhofer Innovation Platform for Drug Discovery and Delivery @ Hebrew University (FIP_DD@HUJI).
Already approved active molecules of the pharmaceutical database DrugBank were pre-selected using computational chemistry. These have the following properties in silico:
- blocking an interaction of the docking molecules of the SARS-CoV-2 virus by binding to the so-called viral spike proteins,
- blocking an interaction at the host cell receptors by blocking the host cell ACE2 proteins, and
- blocking viral 3C-like protease, which has a key role in viral mutation and replication.
When screening 14,245 modeled compounds, 69 potential candidates were identified that possess at least two of the above multi-targeting properties.
Subsequently, the pre-selected active molecules are validated in adapted in vitro test systems. These consist of human cells overexpressing the target receptor ACE2 of the virus or genetically modified reporter cells overexpressing viral spike proteins or 3C-like proteases. Initial in vitro testing confirmed inhibitory effects of the in silico drug candidates.
By combining both methods, in silico design and in vitro testing, we expect that a number of promising molecules will be finally identified for further rapid development towards therapeutic medicine against SARS-CoV-2.