VIGILANT_EU

VIGILANT theme highlighted by Stefan Pöhlmann at the 11th European Meeting on Viral Zoonoses (Saint-Raphaël, Sept 20–23, 2025). Focus: how Sec61 targeting disrupts filovirus glycoprotein function and infectivity.
#ViralZoonoses #EMVZ #SaintRaphael

6. What advice would you give someone interested in science?
Go for it! Science is hard work but you learn new things with every experiment. It’s exciting!

7. What do you hope to achieve next?
Continue to develop vaccines & treatments for diseases with pandemic potential & make VIGILANT a success.

5. Who or what has influenced your scientific journey the most?
My mentors Drs. Manfred Marschall, Stefan Poehlmann and Heinz Feldmann had a big impact on where I am today as a scientist.

3. What excites you most about your work?
Working in the BSL4 and collaborating with many talented scientists around the globe including the VIGILANT team.

4. What’s a discovery or project you’re especially proud of?
My contributions to getting the Ebola virus vaccine by Merck licensed for humans.

2. Briefly, what is your research about?
We study filoviruses, incl. Ebola & Marburg virus, how they interact with the host & cause disease. We also develop and test vaccines & treatments in cell culture & animal models in order to eventually help control filovirus disease outbreaks and save lives.

1. What inspired you to become a scientist?
I had an amazing 5th grade biology teacher who told us about bacteria/viruses - some can be helpful and others make you sick or kill you in days; also viruses do not “live” since they cannot propagate themselves and need a host. I want to understand that.

Andrea Marzi is a German-American virologist whose work focuses on filovirus pathogenesis and the development of VSV-based vaccines against highly pathogenic viruses like Ebola and SARS-CoV-2.

MEET THE VIGILANT TEAM
We are interviewing the staff at Project Vigilant to introduce them to you!

Meet Andrea Marzi
Chief of the Immunobiology & Molecular Virology Section, Laboratory of Virology, DIR, NIAID
National Institutes of Health
Rocky Mountain Laboratories

Mosquito-borne viruses surge in a warming Europe Chikungunya cases break records in France; West Nile virus appears near Rome

climate change - it's a thing. and it affects more than just the climate and weather
www.science.org/content/arti...

Ebola poses a serious global threat. We hope for swift containment and are committed to research for future prevention.

5/
This inhibitor even stopped H7N7 flu replication in cells, offering a promising new lead for antiviral therapy.

4/
When fused to a furin-specific nanobody, the optimized prodomain blocked furin 25,000× more efficiently than its close cousin PCSK5.

3/
Klaushofer et al. turned to a natural brake inside furin itself — its prodomain — and engineered it into a potent, selective inhibitor.

Structural insights into proprotein convertase activation facilitate the engineering of highly specific furin inhibitors Nature Communications - In this work, the authors investigate the activation mechanism of proprotein convertases (PC) based on the PC1/3-prodomain and the PC furin. They engineer a...

2/
@vigilant-eu.bsky.social PI Eva Böttcher-Friebertshäuser contributed to a seminal study tackling this problem.
rdcu.be/eEb6y

1/
The protease furin activates dangerous viruses like H5N1. But since it has many close relatives, specifically targeting furin is a huge challenge.
#Virology #DrugDiscovery

Q6: What is next for you?

WK: To contribute actively to #VIGILANT success and advance pandemic preparedness.

Learn more:
www.lp3.lu.se
www.pps.gu.se/en
www.scilifelab.se/contact/grou...

For a full interview with Wolfgang:
euglohria.eu/euglohria-co...

...research projects. Understanding the function of proteins is not only interesting for understanding fundamental life processes or combating diseases like in #VIGILANT, but also in applied research e.g. developing new energy solutions, sustainable biotechnology or resilient crops in agriculture.

Q5: How can your research help people?

WK: All living organisms are made up of cells that maintain fundamental biochemical reactions. In cells, proteins are pivotal, both as building materials and catalysts for processes of life. Proteins are common targets for drug development and medical ...

Q3: What is your proudest achievement?

WK: To have worked to make protein production a central Lund University infrastructure and Swedish national research infrastructure.

Q4: Who are your mentors?

WK: My PhD and postdoc advisors, Monika Löffler and Jure Piskur, were pivotal influences.

Q2: What excites you most?

WK: Collaborating within an international team, and particularly the drug discovery efforts for S1P in close collaboration with the #VIGILANT principal investigator Torsten Steinmetzer from the Philipps University Marburg.

Q1: What do you see as important in your work?

WK: Protein production is often the first gateway stage in a project. Success require technical knowledge and long-term experience. With our infrastructure, we can provide #VIGILANT with protein production and contribute to structural studies.

Within #VIGILANT, Wolfgang provides recombinant proteins with a focus on one of the main targets for drug discovery of the project: Site-1-Protease (S1P). S1P plays an important role in activation of viral glycoproteins to allow viruses to enter cells and spread infection.

Wolfgang's Science for Life Laboratory is part of the Department of Biology at Lund University in Sweden (www.scilifelab.se/contact/group-leaders/).

Wolfgang's job focus is providing world-class research infrastructure services for protein production and integrated structural biology.

Headshot of Wolfgang Knecht wearing a lab coat and standing in a lab in front of glass refrigerators.

MEET THE VIGILANT TEAM
We are interviewing the staff at Project Vigilant to introduce them to you!

Meet Wolfgang Knecht
Director of the Lund Protein Production Platform (LP3, www.lp3.lu.se), Deputy Director of Protein Production Sweden (PPS, www.pps.gu.se/en) and Group Leader of SciLifeLab.

6/
Still, the potential is huge:
A single drug class that could stop multiple viruses. 🌍💊 That’s why VIGILANT is exploring Sec61 as a new frontline target.

#FuturePandemic #Antivirals #VIGILANT

5/
The challenges ahead:
⚖️ Define how broad the antiviral activity really is
🧬 Investigate if/when viruses can develop resistance
🛡️ Avoid unwanted toxicity, since Sec61 is vital for healthy cells too

Proteolytic processing of the Marburg virus glycoprotein depends on Sec61β and is required for cell entry Ebola and Marburg virus (EBOV, MARV) cause severe disease and therapeutic options are urgently needed. The Sec61 translocon facilitates ER import of viral glycoproteins (GPs) and may represent a thera...

4/
VIGILANT has already shown that a Sec61 inhibitor can block Ebola and Marburg virus in the lab.
www.biorxiv.org/content/10.1...

3/
And here’s the key: Sec61 can be blocked.
Certain small molecules stop the channel and halt protein import. 👇ACS Chemical Biology 2020 15 (8), 2125-2136

2/
For glycoproteins to even reach the ER, they must pass through the Sec61 channel.
Sec61 is like a gate that imports new viral polyprotein chains into the ER.

🔒 If the gate is blocked → no glycoprotein → no infectious virus.