An interdisciplinary research team involving the German Center for Infection Research (DZIF) has identified two antiviral drug candidates effective against a wide range of viruses using a novel computational approach combined with laboratory validation. The study, published in Communications Biology, demonstrates how computer-aided modeling can accelerate the development of broad-spectrum antiviral drugs crucial for pandemic preparedness.
Computational Approach Reveals Viral Vulnerabilities
The international research team from Germany, France, Italy, Greece, and Australia developed computer models representing the complex metabolism of virus-infected cells. Using data from virus-infected tissues, the team created tissue-specific models to simulate the replication of various RNA viruses, which are of particular importance due to their pandemic potential.
"Using these models, we have predicted specific metabolic pathways essential for viral replication, which represent potential targets for antiviral therapies," explains Prof. Dr. Andreas Dräger from Martin Luther University Halle-Wittenberg, who was previously a DZIF scientist at the Institute of Bioinformatics and Medical Informatics at the University of Tübingen.
The modeling revealed metabolic processes that viruses require for replication but that are not essential for cellular survival. The team then searched existing drug databases for substances that inhibit precisely these metabolic processes.
Two Promising Antiviral Candidates Identified
Infection experiments in cell cultures confirmed that two drug candidates—phenformin and atpenin A5—effectively inhibit viral replication across different virus families.
"We then tested this hypothesis experimentally and found various substances with broad antiviral activity against very different virus families," says Prof. Dr. Michael Schindler, Head of the Molecular Virology Section at the Institute of Medical Virology and Epidemiology of Viral Diseases at University Hospital Tübingen.
Phenformin Shows Immediate Clinical Potential
Phenformin, which interferes with cellular metabolism, was previously used as a medication for type 2 diabetes. "Since phenformin is well-characterized for use in humans, our findings could be used to establish supportive therapy against corona or flavivirus infections in the relatively short term," explains Prof. Dr. Christoph Kaleta from the Institute of Experimental Medicine at Kiel University and the University Hospital Schleswig-Holstein.
In animal experiments with SARS-CoV-2-infected hamsters, phenformin significantly reduced the viral load in the respiratory tract. The compound also inhibited the multiplication of dengue viruses in cell cultures, for which there is currently no approved treatment.
Extensive clinical studies on phenformin's use as an antidiabetic agent have already established its safety profile in humans. However, further clinical studies are needed to determine if phenformin has an antiviral effect in humans.
Atpenin A5 Validates Methodological Approach
Atpenin A5, an experimental substance, demonstrates the feasibility of the computational approach in cell culture. Further studies must be conducted to determine whether variants of the substance can be used in animal models where they are both tolerated and have an antiviral effect.
Implications for Pandemic Preparedness
The COVID-19 pandemic has highlighted the urgent need for antiviral drugs with broad spectrum activity—both to treat current infections and to prevent possible new pathogens with pandemic potential. Since most viruses have similar basic replication requirements, the research team suspected that targeting shared metabolic dependencies could inhibit a wide variety of viruses.
According to the scientists, the developed methods and identified drug candidates represent an important step in the rapid development of potential treatments for future pandemics. The approach accelerates the time-consuming identification and development of antiviral agents that could be crucial in the event of future pandemic threats.
