Fraunhofer Institute for Molecular Biology and Applied Ecology IME
Fraunhofer Institute for Molecular Biology and Applied Ecology IME

© Fraunhofer IME

Insect hemolymph of the large wax moth contains new lead structure against influenza

Researchers at the Fraunhofer Institute for Molecular Biology and Applied Ecology in Gießen have identified a promising new approach to combat influenza viruses. A recent study isolated a peptide from the hemolymph of larvae of the Greater Wax Moth (Galleria mellonella) that strongly inhibits the replication of influenza viruses.

 

Background

Influenza, commonly known as "the flu," is a highly contagious respiratory disease caused by influenza viruses. It manifests with symptoms like sudden high fever, body aches, and dry cough, and can lead to severe complications such as pneumonia, particularly in elderly individuals and those with pre-existing conditions. The World Health Organization (WHO) estimates an annual average of 400,000 deaths globally due to seasonal influenza. Current antiviral drugs, such as neuraminidase inhibitors, often face resistance issues as they directly target the virus. Thus, researchers are exploring new treatments that act on conserved viral structures or host factors, which could also be used in combination therapies.

© Fraunhofer IME I Désirée Schulz

 

Antiviral effect of ISPI-2

Research into unused bioresources has the potential to yield a broad spectrum of new antiviral lead structures. As part of the project, a substantial number of bioresources, including fungi and bacteria, have been extracted and examined for their antiviral effect. Of particular interest are insects, which represent a particularly promising bioresource. The hemolymph of insects, which is comparable to human blood, is considered a promising source for a variety of candidates with antibiotic, antifungal and antiviral properties. As the active compounds contained in hemolymph have not yet been studied in detail, our study investigates the antiviral effect of cell-free extracts from the hemolymph of larvae of the greater wax moth. The greater wax moth (Galleria mellonella) is a small butterfly of the moth family. It is considered a dreaded pest in beekeeping, as its larvae can eat and destroy honeycombs. In research, the larvae of the wax moth are used as infection models for microbial pathogens or toxicity studies.

Larvae of the wax moth were extracted using organic solvents. The work deals with the activity-based fractionation of the extracts using the UHLPC-MS/MS pipeline, which yielded several fractions with antiviral activity. Utilising proteome analysis, the peptides ISPI-1 and ISPI-2 (inducible serine protease inhibitor 1 and 2) were identified in the antivirally active fractions. Subsequent to this, ISPI-2 was isolated from the larval extracts using an affinity chromatography process. Enzyme kinetic measurements showed that the peptide inhibits the protease TMPRSS2, which is essential for the replication of influenza viruses. Furthermore, the inhibition of other proteases, such as HAT (human airway trypsin-like protease) and plasmin, was also observed. In cell cultures, ISPI-2 demonstrated the capacity to reduce the replication of a pandemic H1N1 influenza virus subtype by a thousand-fold. The combination of ISPI-2 with the well-known influenza drug oseltamivir proved to be particularly effective. 

 

Outlook

The data suggest that targeting TMPRSS2 is a promising strategy for treating influenza infections. Insects and their antiviral peptides could play a significant role in developing future antiviral drugs. Further research will test ISPI-2 against other respiratory pathogens and assess its efficacy and safety in animal models.

Larvae of the greater wax moth in their final developmental stage.
© Fraunhofer IME
Larvae of the greater wax moth in their final developmental stage.