Biological membranes and macromolecular crowding in the function of the hepatitis C virus proteases
The project goal is to determine the effects of the membrane environment and macromolecular crowders on the structural dynamics and activity of two hepatitis C virus (HCV) proteases. The main hypothesis is that the function of viral proteins depends on the membrane presence and its lipid composition, crowder type and concentration, and the interactions of the substrate with crowders or lipids. We will answer the question how viral enzymes fold and function both near the membranes and in crowded conditions.
We will investigate two enzymes encoded by the HCV genome. This virus causes liver inflammation which can lead to serious liver damage and cancer. There is currently no effective vaccine against hepatitis C, although it is estimated that nearly 200 million people worldwide are affected by HCV. Treatment is available but diagnosis is low because new infections are asymptomatic and the HCV mutates becoming resistant to known therapies.
One of the HCV enzymes that we investigate is called the NS3/4A protease and is a known drug target with several drugs approved for clinical use in the last decade. The second one is the NS2 protease with no approved drugs as yet. These two proteases work at the endoplasmic reticulum membranes of the host cell.
Principal Investigator: prof. dr hab. Joanna Trylska, CeNT UW
PhD student: Małgorzata Lobka, MSc
Project period: 2023 – 2027
Funding: National Science Centre, Preludium BIS 4
