Combating Emerging Viral Threats

The Helmholtz Centre for Infection Research (HZI) is coordinating a pioneering approach to identifying and targeting the crucial virus-cell binding step in viral infections. The COMBINE project seeks to transform how scientists tackle highly pathogenic viruses, such as the Marburg virus, by focusing on their earliest interactions with host cells. 

From the moment a virus binds to and activates a host cell, the stage is set for subsequent internalization and replication. This crucial first step is, therefore, a prime target for therapeutic intervention. However, the process remains understudied due to its complexity and the technical challenges associated with high-containment pathogens.

COMBINE, led by Christian Sieben, head of HZI’s "Nano Infection Biology" group, aims to address this knowledge gap. Using the Marburg virus (MARV) as a model, the project will investigate the mechanisms of virus-cell binding and entry, identifying key molecular players and developing inhibitors that block this process.

Recurrent outbreaks of Marburg infection in previously unaffected regions, and the absence of licensed vaccines or specific antiviral treatments, underscore the urgency of developing robust countermeasures. With a mortality rate often exceeding 50 percent, the Marburg virus remains a significant global health threat.

The COMBINE project employs multidisciplinary methodology, combining advanced molecular biology, proteomics, and drug discovery techniques to analyze and disrupt the virus-cell binding step.

Key objectives of the project include:

• Identifying Molecular Signatures: Using cutting-edge tools to map the proteins and cellular mechanisms involved in viral binding and activation.
• Characterizing Virus-Cell Interactions: Distinguishing between the initial attachment of MARV to host cells and subsequent processes like activation and internalization.
• Developing Novel Therapeutics: Designing inhibitors and vaccine candidates to block MARV entry and prevent infection.

“Our work will not only strengthen the global virology community with new tools and knowledge, but also increase pandemic preparedness by addressing the health threats posed by the Marburg virus and other emerging viral diseases,” said Sieben.

COMBINE represents a shift toward more targeted and mechanistic approaches to antiviral research. By focusing on virus-cell binding, the project opens new avenues for diagnostics, drug discovery, and vaccine development.