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Science for Sapiens A year in research (2024)
he dengue virus is already an endemic
disease in Spain and it is expected that
cases of infection will increase due to pe-
riodic floods that favour the spread of its
vector – the tiger mosquito –. A study by
the University Miguel Hernández of El-
che (UMH), published in the journal Bio-
T chimica Biophysica Acta Biomembranes,
has shown where the virus can interact with human cells
and, therefore, where drugs should be directed to prevent
infection. This finding could be key to avoiding other disea-
ses caused by similar viruses such as Zika and yellow fever.
As Professor of Biochemistry and Molecular Biology at the
UMH José Villalaín – leader of the study – explains, flaviviru-
ses, such as dengue, Zika, West Nile virus or yellow fever, in-
fect human cells by a process called endocytosis. They fuse
their membrane with the cell wall depending on the acidity
they detect. Therefore, knowing this fusion mechanism is
key to obtaining antiviral drugs that prevent infection. Sin-
ce the interaction between viruses and healthy cells occurs
through very complex proteins, in order to understand the
process it is necessary to simulate by computer how the
chemical interaction between their molecules occurs.
Researcher of the Institute for Development, Research and
Innovation in Health Biotechnologies of the University Mi-
guel Hernández (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. Specifically, the dengue
virus, which is already endemic in our country, since auto- Villalaín, J. (2023). Phospholipid binding of the dengue virus envelope E protein
chthonous cases have been detected. According to the re- segment containing the conserved His residue. Biochimica et Biophysica Acta
searcher, it is expected that more and more cases will occur (BBA)-Biomembranes, 184198.
due to high temperatures and periodic floods that favour
the spread of the Aedes aegypti or Aedes albopictus mos-
quitoes, whose bite can transmit the disease. This finding could be
key to avoiding other di-
The new UMH study has shown that a specific sequence of
the protein E of the dengue virus is responsible for both the seases caused by simi-
protein-protein and protein-membrane interaction, funda-
mental in the process of protein activation and the conse- lar viruses such as Zika
quent fusion of viral and cellular membranes. Since mem- and yellowfever
brane fusion is the first and most important step in dengue
virus infection, this discovery is essential to finding an infec-
tion inhibitor.
This study has been carried out using molecular dynamics, targets responsible for viral infections is essential to be able
a process of “virtual simulation” of the interaction between to design antiviral molecules that prevent infections of this
proteins that requires so much computing power that a set type of virus, which are increasingly and unfortunately be-
of computers must be used to carry out the experiment. In coming more recurrent and affect a large part of the popu-
these simulations, you can see how each atom that makes lation”, explains the researcher of the UMH. The additional
up the proteins of the virus behaves, so that both the inte- importance of the new research is that this segment, also
raction between molecules and what happens inside them found in other similar types of viruses, could help find an-
can be studied in detail. For this type of research, the UMH tiviral molecules that would also be effective against den-
has a scientific computing cluster, a group of computers gue-like virus infections, such as Zika or yellow fever.
linked with a high-speed network, managed by the Techno-
logy Innovation and Planning Service. It shows that one of the segments of the protein E of the
dengue virus, besides functioning as a pH sensor, that is,
Previous publications by Professor Villalaín proved that the being able to detect the entry of the virus into the late en-
protein E of the dengue virus, responsible for the entry of dosome, binds to the biomembrane of the cell with a high
the virus into the host cell, has three binding points to bio- affinity and great specificity, which makes it a fundamental
logical membranes. “Finding and defining the therapeutic therapeutic target with which to attack the virus.
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