The interaction between viruses and their host is truly fascinating

"How do viruses enter their host cell and which (receptor) molecules do they hijack for binding? And how can we develop intervention strategies that effectively target the cell entry of viruses? These are the major research questions that we study in my group.

Small viruses, big effects
The intimate interaction between viruses and their host is truly fascinating. Viruses entirely depend on host cells for their replication and reprogramme the cell for their own benefit. As small as they are, as big are the effects these viruses can exert on their host.

Social and economic damage
Viruses constitute a major threat to economies and societies. Veterinary and public health is particularly vulnerable to emerging pathogens that suddenly make their way into the population. Over the past fifteen years, we have encountered quite some emerging or re-emerging viruses. Think of avian influenza, porcine epidemic diarrhea coronavirus (PEDV), SARS and MERS coronavirus, or the Zika virus, just to name a few. All of these agents have caused major social and economic damage.

One Health
My research focuses on coronaviruses. Coronaviruses are important pathogens relevant for veterinary and human health. These viruses are also notorious for their potential to cross the species border. This was demonstrated by the recent emergence of the zoonotic SARS and MERS coronaviruses, so our research is typically One Health. Studying these viruses at the molecular level is crucial to understand various aspects of coronavirus biology, how these viruses evolve, cause disease, cross the species barrier, and to develop novel intervention strategies.

From dromedary camel to humans
We recently discovered that the MERS coronavirus hijacks an evolutionary conserved receptor to bind to target cells that facilitates transmission from the dromedary camel reservoir to humans, together with Bart Haagmans (ErasmusMC). This breakthrough paved the way for subsequent research worldwide providing further important insight in MERS-CoV pathogenesis and development of (transgenic) animal models.

Therapeutic antibodies
We also solved the first high-resolution structures of the viral glycoprotein complex of two coronaviruses that mediates host-cell entry, in collaboration with Felix Rey (Pasteur Institute, Paris) and David Veesler (University of Washington, Seattle). These structures revealed vulnerable and conserved epitopes on these viral glycoproteins that can be used for the development of (broadly reactive) therapeutic antibodies or epitope-based vaccines."

Cell-cell fusion induced by the Spike protein of the (GFP-expressing) porcine coronavirus PEDV (Wicht et al., Journal of Virology 2014).

Often too late...
New viruses will continue to emerge, also enhanced by the increased world population, connectivity of people by traveling, deforestation and climate change. For each newly emerging virus pathogen a specific vaccine has to be developed. The development, manufacturing and registration track for vaccines is currently too time-consuming, so we often run behind the facts when a virus outbreak surfaces. Just think of PEDV, Ebola en Zika...

Universal vaccines
Within an EU-funded consortium of academic and non-academic institutions, we collaborate with pharmaceutical companies to develop a pipeline for fast-track development of vaccines and therapeutic antibodies to be able to faster counteract these emerging viruses. We aim to use our structural insight into viral glycoproteins to develop more universal vaccines that are broadly-reactive against current and potentially future-emerging viruses.

Coronaviruses
We utilise identified vulnerable regions on these glycoproteins that are highly conserved and which the virus cannot easily change because of their critical function. We currently test whether presentation of these isolated domains to the immune system can be used for development of vaccines with broad reactivity against current (and possibly future) emerging coronaviruses.

Tweaking the virulence of viruses
We have also developed systems to manipulate virus genomes to study the function of genes. We apply this expertise to tweak the virulence of viruses so they can be used as live-attenuated virus vaccines."