The Grove Lab
Viral Entry Mechanisms
Enveloped virus particles (such as those of SARS-CoV-2, HIV and Hepatitis C) possess entry glycoproteins that are responsible for engaging with host cells and mediating fusion of host and viral membranes. Probably the most (in)famous example of a viral entry glycoprotein is SARS-CoV-2 spike. Understanding the molecular mechanics of these proteins informs on fundamental biology, immune evasion, virus evolution and vaccine design.
We are currently investigating virus entry by Hepatitis C virus and SARS-CoV-2. There are ~70 million people living with HCV worldwide, and there is currently no vaccine to prevent ongoing transmission of HCV. SARS-CoV-2 continues to cause a global health crisis, a situation that has been exacerbated by the emergence of new viral variants.
We are addressing two over-arching questions:
- How do the HCV entry glycoproteins work? Answering this question will reveal fundamental biology and guide the design of HCV vaccines.
- How is the entry mechanism of SARS-CoV-2 altered in recently emergent variants? Answering this question will inform on the evolutionary trajectory of SARS-CoV-2 and allow us to consider what the virus might do next.
Our recent work suggests that protein disorder plays an important role in regulating entry by SARS-CoV-2 and HCV. We are using both systems to develop fundamental concepts around how viruses harness protein disorder and sequence diversity to fine tune and control their entry machineries.
- CVR – Prof. David Bhella
- CVR – Prof. David Robertson
- CVR – Dr. Rob Gifford
- Birkbeck – Prof. Adrian Shepherd