Nature Communications - A human monoclonal antibody blocking SARS-CoV-2 infection

[Gert van der Hoek]

• Chunyan Wang,
• Wentao Li,
• Dubravka Drabek,
• Nisreen M. A. Okba,
• Rien van Haperen,
• Albert D. M. E. Osterhaus,
• Frank J. M. van Kuppeveld,
• Bart L. Haagmans,
• Frank Grosveld &
• Berend-Jan Bosch

Nature Communications volume 11, Article number: 2251 (2020) Cite this article

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Abstract

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking.

Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture.

This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.

 

[Gert van der Hoek]

“This research builds on the work our groups have done in the past on antibodies targeting the SARS-CoV that emerged in 2002/2003,” said Berend-Jan Bosch, Associate Professor, Research leader at Utrecht University, and co-lead author of the Nature Communications study. “Using this collection of SARS-CoV antibodies, we identified an antibody that also neutralizes infection of SARS-CoV-2 in cultured cells. Such a neutralizing antibody has potential to alter the course of infection in the infected host, support virus clearance or protect an uninfected individual that is exposed to the virus.”

 

[Gert van der Hoek]

See also:

Scientists from Erasmus MC and Utrecht University claim the discovery of an antibody against Covid-19

A human monoclonal 1 antibody blocking SARS-CoV-2 infection

 

[Gert van der Hoek]

Scientists Create Antibody That Defeats Coronavirus in Lab

4 mei 2020

• Antibody known as 47D11 prevented Covid-19 and SARS in study
• Early findings made in the lab may not be confirmed in humans

........................................

Monoclonal antibodies are lab-created proteins that resemble naturally occurring versions the body raises to fight off bacteria and viruses. Highly potent, they target exactly one site on a virus. In this case, the scientists used genetically modified mice to produce different antibodies to the spike proteins of coronaviruses. After a subsequent screening process, 47D11 emerged as showing neutralizing activity. Researchers then reformatted that antibody to create a fully human version, according to the paper.

“Monoclonal antibodies targeting vulnerable sites on viral surface proteins are increasingly recognized as a promising class of drugs against infectious diseases and have shown therapeutic efficacy for a number of viruses,” Bosch and colleagues wrote.

Monoclonal antibodies already sparked a treatment revolution in cancer, with medicines such as Merck & Co.’s Keytruda and Roche Holding AG’s Herceptin becoming some of the world’s bestsellers. AbbVie Inc.’s blockbuster inflammation treatment Humira is also part of the monoclonal antibody family.

Two such antibody therapies show promise against Ebola. Companies such as Regeneron Pharmaceuticals Inc. are also working on possible antibody treatments for the coronavirus.

 

[gsgs]

https://www.biorxiv.org/content/10.1...958v1.full.pdf

I can't quickly find the amino-acid sequence, is it secret ?

SARS-RBD 323 CPFGEVFNATKFPSVYAWERKKISNCVADYSVLYNSTFFSTFKCYGVSAT KLNDLCFSNV
SARS2-RBD 438 CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPT KLNDLCFTNV
**********:* *****:**:**************: ********** ********:**
SARS-RBD 383 YADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNIDATS TGNYNYKYRY
SARS2-RBD 396 YADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKV GGNYNYLYRL
******::**:********** ************ ***:***:.*:*:. ***** **
SARS-RBD 443 LRHGKLRPFERDISNVPFSPDGKPCTP-PALNCYWPLNDYGFYTTTGIGYQPYRVVVLSF
SARS2-RBD 456 FRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGY QPYRVVVLSF
:*:.:*:*******. :. ...**. .:***:**:.*** *.*:************
SARS-RBD 502 ELLNAPATVCGP
SARS2-RBD 516 ELLHAPATVCGP
***:********


But the structure of this motif is surprisingly different in SARS-CoV-1 and SARS-CoV-2, Wang says.
Whereas overall the amino acid sequences that make up the spike protein are about 80 percent
identical between the two viruses, their receptor binding motifs are only around 50 percent the same.


https://theweek.com/articles/904095/closing-new-coronavirus

 

[JJackson]

gs
I am not sure they know what the sequence is. They assume it is binding somewhere on S1b, but not on the RBD, and does not stop ACE2 binding. I don't think they know how it works, only that it does, and that it reduces SARS-2's ability to cause cell to cell fusion. I thought about it but could not think of an obvious route. If it causes a conformational change it could block cleavage or interfere with the change in structure induced by cleavage needed for endocytosis. But if it really is locked out then how is it blocking synsytia? I assumed this was due to one of the ORF1ab polyprotein's non-structural proteins whose primary function is to mess with the cellular pathways including blocking the intra-cellular innate immune defenses like IFNa.