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Topic: Looking For a Molecular Virucidal KeyPosted By: Technophobe
Subject: Looking For a Molecular Virucidal Key
Date Posted: April 27 2018 at 6:33am
Public Release:
Transplant-damaging virus comes into focus
University of Leeds
Researchers from the University of Leeds have
revealed the structure of a virus which affects kidney and bone marrow
transplant patients in near-atomic levels of detail for the first time.
This detailed information serves as a molecular-level structural
visualisation, allowing scientists to study several potential targets
for antiviral therapies or drugs.
IMAGE: The structure of the BK Polyomavirus produced by the Astbury Centre researchers at the University of Leeds.
https://www.eurekalert.org/multimedia/pub/168988.php" rel="nofollow - view - more
Credit: University of Leeds
In order to create a drug which can target viruses, researchers need
to know what the virus looks like. With this knowledge, they can target
chemical compounds at it in such a way that they bond with it
precisely, stopping the virus from working. The more detailed the
structure they have to work with, the more precision they can apply.
The research team at the University's Astbury Centre for Structural
Molecular Biology focused on the infectious BK polyomavirus (BKV), using
the centre's two cryo-electron microscopes to develop the incredibly
detailed imaging required.
A research paper announcing the new structures has been published in the journal Structure.
The level of detail in the image allows scientists to see features on
the virus as tiny as ~3 Ångströms wide. One Ångström is equivalent to
one ten-billionth of a metre or 0.1 nanometre. The structure is so small
it cannot be seen by the naked eye.
Astbury Centre PhD researcher Dan Hurdiss, lead author of the paper,
said: "Our structures provide the clearest picture to date of the
infectious virus particle. This detailed information serves as a
structural roadmap, allowing us to visualise several potential targets
for antiviral therapies.
"These may include drugs which block BKV from entering our cells or
which prevent proper assembly of the virus particle. Going forward,
these structures may also be used to identify how antibodies from
patients with other diseases recognise the BKV virus particle and thus
aid in the development of a vaccine."
About 80% of the world's adult population is infected with BKV, but
the virus rarely causes illness in people with a healthy immune system.
However, in immunocompromised individuals, BKV can 'reactivate' and
cause serious diseases.
Two such examples of BKV-associated diseases are
polyomavirus-associated nephropathy (PVAN) and haemorrhagic cystitis
(HC) which affect kidney and bone marrow transplant recipients
respectively.
Around 10% of people who receive a kidney transplant will suffer
from PVAN and up to 90% of these will go on to have their transplant
organs rejected. At present, there are limited treatment options
available for individuals suffering from BKV associated diseases.
The new structures will give hope to sufferers, by giving scientists a better-quality research tool to work with.
The structures were created using the cryo-electron microscopy
method, by freezing infectious BKV particles and taking thousands of
images using the microscopes. These two-dimensional images were then
combined computationally to produce a high-resolution, three-dimensional
view of the virus.
Professor Neil Ranson, Director of Cryo-Electron Microscopy at the
University of Leeds, said: "Cryo-electron microscopy has been around for
30 years and has been incredibly useful, but until recently the
technology lacked the ability to routinely look at molecules at the
level of detail needed.
"Without that detail, scientists sometimes struggled to understand
the structure of biological molecules and how they function, especially
when they are in their normal workplace: inside our cells.
"However, the Titan Krios microscopes we have installed in Leeds are
absolutely state-of-the-art, and mean that these limitations have been
shattered. Researchers and industry users who work with us can now image
biological molecules with an incredible resolution. Crucially, we'll
also be able to see how these molecules interact with each other."
###
The BK Polyomavirus structure research was funded by Wellcome, Kidney Research UK and Kidney Research Yorkshire.
Further information
Journalists with questions or interview requests, or who would like
to visit the University's cryo-electron microscopy suite should contact
Peter Le Riche in the University of Leeds press office on 0113 343 2049
or email mailto:p.leriche@leeds.ac.uk" rel="nofollow - p.leriche@leeds.ac.uk
Photos and film footage of the microscopes is also available, as is a copy of the BK polyomavirus structure.
The DOI number of the research paper is DOI:
10.1016/j.str.2018.03.019, it will be live after the article is
published 12.00pm EST / 5pm UK time on 26 April 2018.
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not responsible for the accuracy of news releases posted to EurekAlert!
by contributing institutions or for the use of any information through
the EurekAlert system.
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