VIGILANT Project

Targeting ER Import and Activation of Viral Glycoproteins: Towards Broad-Spectrum Antivirals

The EU research consortium VIGILANT is developing broad-spectrum drugs targeting viruses with pandemic potential. Coordinated by the German Primate Center – Leibniz Institute for Primate Research, the project is funded by the EU with approximately 7.5 million euros over four years.

The goal of VIGILANT is to develop compounds that are effective against a wide range of viruses and thus contribute to combating future pandemic threats. These compounds are designed to specifically block the transport of viral envelope proteins into the endoplasmic reticulum of infected cells, as well as their subsequent activation by host cell enzymes. The efficacy and safety of the candidate compounds will be tested in cell culture models and animal studies.

Funded by the EU - Horizon Europe Grant no. 101191811.

Partners

Work Packages

Work Package 1 - Inhibitors of the Sec61 translocon

The goal is to identify Sec61 inhibitors that effectively prevent infection of cells by emerging viruses. In addition, the project aims to investigate the basis of the virus-specific activity of these inhibitors and whether viruses can develop resistance to them.

Lead Researcher: Prof. Dr. Ville Paavilainen

Work Package 2 - Protease usage, cleavage sites and mechanism

The goal is to elucidate the activation of filovirus glycoproteins by host cell proteases, with a particular focus on proprotein convertases. In addition, the influence of Sec61 channel components on glycoprotein cleavage will be analyzed.

Lead Researcher: Prof. Dr. Stefan Pöhlmann

Work Package 3 - Design, synthesis and optimization of protease inhibitors

The goal is to produce and comprehensively characterize new and existing inhibitors of Furin, SKI-1, and Cathepsin B/L. In addition, recombinant SKI-1 will be crystallized to use the structural information for the targeted optimization of inhibitors.

Lead Researcher: Prof. Dr. Torsten Steinmetzer

Work Package 4 - Preclinical models: Cell line, organoid and rodent models

The goal is to investigate the antiviral efficacy of Sec61 and protease inhibitors in cell lines and to analyze potential resistance development. In addition, the antiviral activity of these inhibitors will be evaluated in organoid and rodent models.

Lead Researcher: Dr. Sandra Diederich

Work Package 5 - Preclinical models: Ferret and NHP models

The goal is to investigate the antiviral activity of protease inhibitors in macaque models for emerging viruses.

Lead Researcher: Prof. Dr. Andrea Marzi

Work Package 6 - Proteases as novel restriction and dependency factors

The goal is to identify proteases involved in viral entry and later stages of infection using RNAi screens and transcriptome profiling.

Lead Researcher: Prof. Dr. Eva Böttcher-Friebertshäuser

Public Deliverables

D1.3 - Sec61-inhibitor structures

Structure of Sec61 bound to inhibitors, deposited to PDB, EMDB and EMPIAR databases.

This deliverable is not yet complete.

D3.5 - SKI-1 crystal structures

Deposition of available crystal structures at PDB.

This deliverable is not yet complete.

D7.1 - Press release

A press release announcing the project launch has been published.

This can be found under https://www.dpz.eu/en/public-engagement/news/article/neues-eu-forschungsprojekt-entwickelt-breitbandmedikamente-gegen-viren.

D7.2 - Consortium website established

Website (incl. name, logo, project description, partner information, news, and upcoming events) online.

D7.3 - Social media

Set up of social media accounts like X (Twitter), ResearchGate, LinkedIn.

This deliverable is not yet complete.

D7.4 - Scrollytelling

Interactive, web-based, laylanguage, multimedia information to public.

This deliverable is not yet complete.

Events

Stefan Pöhlmann welcomes the project partners and outlines the focus of the project.

Kick-Off Meeting

The kick-off meeting on Friday, March 7, 2025, was a great success. Scientific partners from all participating institutions across the EU traveled to Göttingen, joined by a partner from the USA who participated online, for an afternoon of introductions and scientific exchange.

Kick-Off Meeting - planned for 7th March, 2025

The first event of the VIGILANT project, the kick-off meeting, will take place on Friday, 7th March, 2025 at the DPZ. All project partners from Europe and the USA are invited to attend.