Nsp15 inhibitors for preventing future viral pandemics (Nsp15 VIPA)
Project leader: Prof. Dr. Oliver Plettenburg
Key area
- Antiviral strategies: agents and vaccines, antibodies
Who is involved?
- Prof. Dr. Oliver Plettenburg (Project leader, Leibniz University Hannover)
- Prof. Dr. Mark Brönstrup (HZI)
- Prof. Dr. Ulrich Kalinke (TWINCORE)
- Prof. Dr. Maren von Köckritz-Blickwede (TiHo)
International cooperation partners:
- Carsten Schultz (Oregon Health and Science University, Portland, USA)
- Fikadu Tafesse (Oregon Health and Science University, Portland, USA)
What is the aim?
The importance of the highly conserved protein Nsp15 for the infection of cells by coronaviruses has been studied in detail in recent years. As an endonuclease, it rapidly recognises and degrades both single-stranded (ssRNA) and double-stranded RNA (dsRNA). In addition, evidence from animal models suggests immunomodulatory properties of Nsp15 during early viral infection, leading to a delayed immune response. This process is ultimately involved in the development of acute lung failure, which is the major cause of COVID-19 mortality. In this funding programme, we plan to develop new inhibitors of this protein through structure-guided design. Promising compounds will be characterised in terms of their ADME and physicochemical properties to provide orally bioavailable compounds for the treatment of future viral pandemics.