Engineered llama antibodies neutralize COVID-19 virus

Date:
July 13, 2020
Source:
The Rosalind Franklin Institute
Summary:
Antibodies derived from llamas have been shown to neutralise the
SARS- CoV-2 virus in lab tests, researchers have found. They hope
the antibodies -- known as nanobodies due to their small size --
could eventually be developed as a treatment for patients with
severe COVID-19.



FULL STORY ========================================================================== Antibodies derived from llamas have been shown to neutralise the SARS-CoV-
2 virus in lab tests, UK researchers announced today.


==========================================================================
The team involves researchers from the Rosalind Franklin Institute,
Oxford University, Diamond Light Source and Public Health England. They
hope the antibodies -- known as nanobodies due to their small size --
could eventually be developed as a treatment for patients with severe
COVID-19. The peer reviewed findings are published in Nature Structural & Molecular Biology.

Llamas, camels and alpacas naturally produce quantities of
small antibodies with a simpler structure, that can be turned into
nanobodies. The team engineered their new nanobodies using a collection
of antibodies taken from llama blood cells. They have shown that the
nanobodies bind tightly to the spike protein of the SARS-CoV-2 virus,
blocking it from entering human cells and stopping infection.

Using advanced imaging with X-rays and electrons at Diamond Light Source
and Oxford University, the team also identified that the nanobodies
bind to the spike protein in a new and different way to other antibodies already discovered.

There is currently no cure or vaccine for COVID-19. However, transfusion
of critically ill patients with serum from convalesced individuals, which contain human antibodies against the virus, has been shown to greatly
improve clinical outcome. This process, known as passive immunisation,
has been used for over 100 years, but it is not straightforward to
identify the right individuals with the right antibodies and to give
such a blood product safely. A lab-based product which can be made on
demand would have considerable advantages and could be used earlier in
the disease where it is likely to be more effective.

Professor James Naismith, Director of The Rosalind Franklin Institute
and Professor of Structural Biology at Oxford University said: "These nanobodies have the potential to be used in a similar way to convalescent serum, effectively stopping progression of the virus in patients who
are ill. We were able to combine one of the nanobodies with a human
antibody and show the combination was even more powerful than either
alone. Combinations are particularly useful since the virus has to change multiple things at the same time to escape; this is very hard for the
virus to do. The nanobodies also have potential as a powerful diagnostic." Professor Ray Owens from Oxford University, who leads the nanobody program
at the Franklin, said: "This research is a great example of team work
in science, as we have created, analysed and tested the nanobodies in 12
weeks. This has seen the team carry out experiments in just a few days,
that would typically take months to complete. We are hopeful that we can
push this breakthrough on into pre-clinical trials." Professor David
Stuart, from Diamond Light Source and Oxford University said: "The
electron microscopy structures showed us that the three nanobodies can
bind to the virus spike, essentially covering up the portions that the
virus uses to enter human cells." The team started from a lab-based
library of llama antibodies. They are now screening antibodies from
Fifi, one of the 'Franklin llamas' based at the University of Reading,
taken after she was immunised with harmless purified virus proteins.

The team are investigating preliminary results which show that Fifi's
immune system has produced different antibodies from those already
identified, which will enable cocktails of nanobodies to be tested
against the virus.

The Rosalind Franklin Institute is a new research institute funded
through UK Research and Innovation's Engineering and Physical Sciences
Research Council.

The Franklin is leading the UK's work in the innovative field of
nanobodies, whose tiny size and specificity make them perfect tools for scientific research, usually used to stabilise proteins for imaging. The Institute is named for the researcher Rosalind Franklin, who was born
100 years ago this year. Although famous for her contribution to the
discovery of DNA, Franklin's later career turned to imaging virus
structures, including polio.

Professor Naismith said: "2020 marks the centenary of Franklin's birth. As
an institute named for a pioneer of biological imaging, we are proud to
follow in her footsteps and continue her work in viruses, applied here
to an unprecedented global pandemic. Franklin's work transformed biology,
and our projects aspire to that same transformational effect."

========================================================================== Story Source: Materials provided by The_Rosalind_Franklin_Institute. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jiangdong Huo, Audrey Le Bas, Reinis R. Ruza, Helen
M. E. Duyvesteyn,
Halina Mikolajek, Tomas Malinauskas, Tiong Kit Tan, Pramila
Rijal, Maud Dumoux, Philip N. Ward, Jingshan Ren, Daming Zhou,
Peter J. Harrison, Miriam Weckener, Daniel K. Clare, Vinod
K. Vogirala, Julika Radecke, Lucile Moynie', Yuguang Zhao, Javier
Gilbert-Jaramillo, Michael L.

Knight, Julia A. Tree, Karen R. Buttigieg, Naomi Coombes, Michael J.

Elmore, Miles W. Carroll, Loic Carrique, Pranav N. M. Shah, William
James, Alain R. Townsend, David I. Stuart, Raymond J. Owens,
James H.

Naismith. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and
block interaction with ACE2. Nature Structural & Molecular Biology,
2020; DOI: 10.1038/s41594-020-0469-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200713104334.htm

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