Synergistic inhibition of SARS-CoV-2 replication by pyrimidine analogues and inhibitors of pyrimidine synthesis
Project leader: Prof. Dr. med. Matthias Dobbelstein
Key area
- Antiviral strategies: agents and vaccines, antibodies
Who is involved?
- Prof. Dr. med. Matthias Dobbelstein (Project leader, UMG)
- Prof. Dr. Maren von Köckritz-Blickwede (TiHo)
- Prof. Dr. Asisa Volz (TiHo)
What is the aim?
We are evaluating the combination of two pharmacological strategies against SARS-CoV-2 replication. On the one hand, we treat with molnupiravir, a cytidine analogue that is spuriously incorporated into viral RNA. On the other hand, we prevent the cells from synthesising their own pyrimidine bases by inhibiting the enzyme DHODH. The synergistic effect of these two approaches will be tested in cell and animal models to develop a treatment approach against COVID-19.
Publications
- Inhibitors of dihydroorotate dehydrogenase cooperate with Molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication. Kim M. Stegmann , Antje Dickmanns , Natalie Heinen, Claudia Blaurock, Tim Karrasch , Angele Breithaupt, Robert Klopfleisch, Nadja Uhlig, Valentina Eberlein, Leila Issmail, Simon T. Herrmann, Amelie Schreieck, Evelyn Peelen, Hella Kohlhof, Balal Sadeghi, Alexander Riek, John R. Speakman, Uwe Groß , Dirk Görlich, Daniel Vitt, Thorsten Müller, Thomas Grunwald, Stephanie Pfaender, Anne Balkema-Buschmann, and Matthias Dobbelstein. IScience, 104293. doi.orghttps://doi.org/10.1016/j.isci.2022.104293