A team of scientists has created a computer simulation of an enzyme called NS3 that
plays an important role in helping the hepatitis C virus replicate and spread in the body.
The discovery should aid the search for drugs that uniquely target the virus.
The image shows the enzyme NS3 in action on unraveling viral RNA.
Image credit: SISSA
The scientists, from the International School of Advanced Studies (SISSA) in
Trieste, Italy, describe their work in the journal Nucleic Acids Research.
As scientists begin to understand more about how a particular virus replicates, the better the chances of finding
drugs that stop the virus spreading.
The team decided to analyze NS3 because it is specific to the hepatitis C virus. They note that a drug
that targets the enzyme selectively would not cause side effects in the rest of the body.
But to be able to target NS3, scientists need to know more about how it behaves. So far, the only
knowledge has come from snapshots – still images – of the enzyme obtained through
crystallography studies.
The new computer simulation offers researchers the first ever opportunity to observe NS3
behavior as if watching a moving film.
NS3 is a helicase – an enzyme that interacts with the virus’ RNA (viruses do not have DNA,
their genetic code is held in RNA).
NS3 ‘crawls along the viral RNA like a caterpillar’
NS3 helps to unravel and prepare the viral DNA for replication, a process that involves a
second enzyme called polymerase. First author and SISSA student Andrea Pérez-Villa explains:
“NS3 crawls along the RNA strand contracting and extending like a caterpillar and,
as it does so, it releases the part of the virus to which the polymerase then
attaches.”
The team’s computer simulation shows not only how NS3 interacts with viral RNA, but also
how the process uses ATP – the chemical units of energy that proteins consume as they do
their work.
Senior author Giovanni Bussi, professor and head of a SISSA group that makes computer
simulations to study RNA, says their model reproduces the “interaction with ATP and
subsequently with ADP, a waste product together with phosphate, after ATP had been utilized.”
He concludes:
“By knowing in detail how this helicase works, in the future we could try to
block the viral replication, and thus stop the disease from proliferating in the
body.”
The following series of videos from SISSA shows the computer simulation of NS3
interacting with viral DNA.
According to the World Health Organization (WHO), 130-150 million people worldwide have chronic
hepatitis C infection and around half a million people die every year from a liver disease
related to the infection.
Meanwhile, Medical News Today recently reported how scientists have discovered a group of liver-regenerating cells that can replenish
damaged liver tissue without producing dangerous tumors.
Written by Catharine Paddock PhD
Copyright: Medical News Today
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