Ultrapotent antibody mix blocks COVID-19 virus attachment

Date:
September 25, 2020
Source:
University of Washington Health Sciences/UW Medicine
Summary:
A cocktail of powerful antibodies identified in recovered patients
locks the coronavirus infection machinery, inhibits SARS-CoV-2
attachment to host cells, and protects animals challenged with
the pandemic coronavirus.



FULL STORY ==========================================================================
A mix of ultrapotent antibodies from recovered COVID-19 patients has been
shown to recognize and lock down the infection machinery of the pandemic coronavirus and keep it from entering cells. Each of the antibody types performs these overlapping tasks slightly differently.


==========================================================================
Low doses of these antibodies, individually or as a cocktail, were also
shown to protect hamsters from infection when exposed to the coronavirus
by preventing it from replicating in their lungs.

An advantage of such cocktails is that they might also prevent the
natural mutant forms of the virus that arose during this pandemic to
escape treatment.

As some variants in the infection machinery have already been discovered
during the coronavirus pandemic, using a mix of antibodies allows for neutralization of a broad spectrum of such viral variants.

In addition to preventing virus entry into host cells, the presence of
the antibodies also seems to set off the infection-fighting actions of
other immune cells, which arrive to clear out the virus.

"We believe that leveraging multiple, distinct, complementary mechanisms
of action could provide additional benefits for clinical applications,"
the researchers noted.

The researchers determined how the antibodies worked on a molecular
level through cryo-electron microscopy studies of the resulting changes
in the configuration of the virus infection machinery. Besides directly preventing interactions with the host receptor, one of the two discovered antibodies locks the infection machinery in an inactive conformation,
meaning it could not fuse with the host membrane on the surface of the
cell. If unable to fuse, the coronavirus cannot break in and deliver
its RNA to commandeer the cell.

The findings of this research are reported Sept. 24 in a rapid release
paper in Science.

The senior authors were Dr. Katja Fink of Vir Biotechnology and Dr. David Veesler, associate professor of biochemistry at the University of
Washington School of Medicine. Veesler has studied the molecular structure
and infection mechanisms of a variety of coronaviruses and other viruses.

The lead authors were M. Alejandra Tortorici of the UW Department
of Biochemistry and the Institut Pasteur in Paris, and Martina
Beltramello of Humab BioMed, a subsidiary of Vir Biotechnology in
Switzerland. Researchers from Washington University in St Louis, Rega
Institute in Belgium, the University of Milan, Italy, and the University
of Texas in Dallas also collaborated on the research.

Efficient therapeutic options are needed to control the spread of
SARS-CoV- 2 that has caused more than 978,000 fatalities worldwide. While
the world awaits approved vaccines, pharmaceuticals to prevent or treat infections from the pandemic coronavirus are being sought that might
be quicker to develop and test. These might both address the gap until
vaccines are widely distributed, and still be needed for use after
vaccines are available.

"Our results pave the way to implement antibody cocktails for prophylaxis
or therapy that might have the advantage of circumventing or limiting the emergence of viral escape mutants," the researchers noted. The antibody cocktail in their study needs to undergo trials in humans to determine
safety and effectiveness.

This study was supported by the National Institute of General Medical
Sciences, the National Institute of Allergy and Infectious Diseases,
a Pew Biomedical Scholars Award, an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund, Fast Grants,
the University of Washington Arnold and Mabel Beckman cryoEM center, the Pasteur Institute, the KU Leuven/UZ Leuven COVID-19 Fund, the Flanders
Fonds voor Wetenschappelijk Onderzoek, and the Bill and Melinda Gates Foundation.


========================================================================== Story Source: Materials provided by University_of_Washington_Health_Sciences/UW_Medicine.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. M. Alejandra Tortorici, Martina Beltramello, Florian A. Lempp, Dora
Pinto, Ha V. Dang, Laura E. Rosen, Matthew McCallum, John Bowen,
Andrea Minola, Stefano Jaconi, Fabrizia Zatta, Anna De Marco,
Barbara Guarino, Siro Bianchi, Elvin J. Lauron, Heather Tucker,
Jiayi Zhou, Alessia Peter, Colin Havenar-Daughton, Jason
A. Wojcechowskyj, James Brett Case, Rita E.

Chen, Hannah Kaiser, Martin Montiel-Ruiz, Marcel Meury, Nadine
Czudnochowski, Roberto Spreafico, Josh Dillen, Cindy Ng, Nicole
Sprugasci, Katja Culap, Fabio Benigni, Rana Abdelnabi, Shi-Yan
Caroline Foo, Michael A. Schmid, Elisabetta Cameroni, Agostino Riva,
Arianna Gabrieli, Massimo Galli, Matteo S. Pizzuto, Johan Neyts,
Michael S.

Diamond, Herbert W. Virgin, Gyorgy Snell, Davide Corti, Katja
Fink, David Veesler. Ultrapotent human antibodies protect against
SARS-CoV- 2 challenge via multiple mechanisms. Science, 2020;
eabe3354 DOI: 10.1126/science.abe3354 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200925113427.htm

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