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Project A4: Maximilian Große, doctoral researcher (PhD, Alumnus)

Antiretroviral therapy with amendment of HIV-1-specific T-cell response

In the last two decades, three coronaviruses, SARS-CoV, MERS, and very recently, SARS-CoV-2 emerged from the animal kingdom, causing in each case life-threatening diseases, particularly as non-immunocompetent populations were encountered. Since there is no approved antiviral therapy available for SARS-CoV-2 infection, the medical need to prevent the transition of a mild into the severe COVID-19 stage of infection is of outmost importance. Therefore, I try to find new small molecule interventions for the treatment of SARS-CoV-2. The focus are cellular targets, which are crucial for virus replication. Thereby, there are two advantages in comparison to direct acting agents (DAAs), targeting viral proteins: i) general mechanisms on which viruses depend are affected and thus a broad range of different virus variants is blocked, ii) cellular targets are, in contrast to the viral ones, genetically stable and thus the risk for the development of drug resistances is significantly lower. My work focusses on components of the ubiquitin proteasome system (UPS) which seem to be, beside other viruses, also crucial for coronaviruses. The research of my supervising lab has been focused on Inhibitors of the proteasome (PIs) and deubiquitinating enzymes (DUBs; DIs) which have a broad antiviral activity.