A virtual analysis of the dengue virus carried out at the UMH finds a therapeutic target to prevent infection

ALICANTE, July 26. (EUROPEAN PRESS) -

A study by the Miguel Hernández University (UMH) in Elche (Alicante) has shown the specific place on the virus to interact with human cells and, therefore, where drugs should be targeted to prevent dengue infection. This finding could be key to avoiding other diseases caused by similar viruses such as Zika and yellow fever.

The dengue virus is already an endemic disease in Spain, as autochthonous cases have been detected and cases of infection are expected to increase due to periodic floods that favor the spread of its vector, the tiger mosquito, as reported by the academic institution on Wednesday. it's a statement.

As explained by the professor of Biochemistry and Molecular Biology at the UMH José Villalaín, leader of the study, which has been published in the journal Biochimica Biophysica Acta Biomembranes, flaviviruses, such as dengue, Zika, West Nile virus or yellow fever they infect human cells by a process called endocytosis, which consists of fusing their membrane with the cell wall depending on the acidity they detect.

Knowing this fusion mechanism is "key" to obtain antiviral drugs that prevent infection, according to the UMH. Since the interaction between viruses and healthy cells occurs through very complex proteins, in order to understand the process it is necessary to simulate on a computer how the chemical interaction between its molecules occurs.

The researcher at the Institute for Development, Research and Innovation in Health Biotechnologies of the Miguel Hernández University (IDiBE) José Villalaín has applied virtual analysis to study one of the "most important" health threats that Spain has in general and the Valencian Community in particular: flavivirus infections.

According to the researcher, it is to be expected that there will be more and more cases due to the high temperatures and periodic floods that favor the extension and propagation of the Aedes aegypti or Aedes albopictus mosquitoes, whose bites can transmit the disease.

The new UMH study has shown that a specific sequence of the E protein of the dengue virus is responsible for both protein-protein and protein-membrane interaction, essential in the process of protein activation and in the consequent fusion of viral membranes. and cell. Since membrane fusion is the first and most important step in dengue virus infection, this discovery is essential to find an infection inhibitor.

This study has been carried out using molecular dynamics, a process of "virtual simulation" of the interaction between proteins that requires so much computing power that a set of computers has to be used to carry out the experiment. In these simulations, you can see how each atom that makes up the virus proteins behaves, so you can study in detail both the interaction between molecules and what happens within them.

For this type of research, the UMH has a scientific computing cluster, a group of computers linked by a high-speed network, managed by the Technological Innovation and Planning Service.

Previous publications by Professor Villalaín demonstrated that the E protein of the dengue virus, responsible for the entry of the virus into the host cell, has three binding points to biological membranes. "Finding and defining the therapeutic targets responsible for viral infections is essential to be able to design antiviral molecules that prevent infections with this type of virus, which unfortunately is becoming more and more recurrent and affecting a large part of the population", explains the UMH researcher.

The additional importance of the new work lies in the fact that this segment, also found in other similar types of viruses, could help to find antiviral molecules that would also be effective against dengue-like virus infections, such as Zika or yellow fever.

It shows that one of the segments of the E protein of the dengue virus, in addition to functioning as a pH sensor, that is, being capable of detecting the entry of the virus into the late endosome, binds to the biomembrane of the cell. with high affinity and great specificity, which makes it a "fundamental" therapeutic target with which to attack the virus.