COR-101 is Inhibiting the Emerging “Indian” Variants of SARS-CoV-2 including “Delta”

The human recombinant anti-SARS-CoV-2 antibody COR-101 was developed in close cooperation of Technische Universität Braunschweig, the Helmholtz Centre for Infection Research (HZI) and the biotech company YUMAB GmbH in Braunschweig. The antibody is currently undergoing phase Ib/II clinical trials for the treatment of moderate to severe COVID-19 by CORAT Therapeutics GmbH. The story of the discovery and development of this antibody was now published in the Journal “Cell Reports”.

In the first step, the genetic information of immune cells, which are producing anti-SARS-CoV-2 antibodies, was isolated from blood samples from local convalescent COVID-19 patients. The collected antibody genes are used for the construction of a phage display library. Nearly 200 unique human antibodies binding to the Receptor Binding Domain (RBD) in the spike protein of SARS-CoV-2 were discovered in the test tube using the phage display approach. In tests performed at the BSL-3 facilities of the Helmholtz Centre for Infection Research (HZI), 30 of these antibodies efficiently blocked the infection of cells with patient-isolated SARS-CoV-2. Antibody COR-101 showed the best neutralization activity.

The efficacy of the antibody was confirmed in transgenic mice, which express the human ACE2 receptor, and syrian hamsters. Virus loads in the deep lung were efficiently reduced or completely eliminated. The atomic structure of the antibody in complex with the RBD was determined and shows that the antibody directly and broadly blocks the interaction of the RBD with the human ACE2 receptor. Significantly, COR-101 binds and inhibits the spike proteins of most recently emerging SARS-CoV-2 variants, including the “Indian“ variants (B.1.617.1 and .3). New additional data, generated after publication in Cell Reports, indicate that even the most recent WHO variant of concern, B.1.617.2 („delta“), is also efficiently inhibited.

In contrast to the antibodies, which got an emergency use authorization in the EU and are designed for the treatment of not hospitalized patients with mild symptoms, the antibody COR-101 is made to treat COVID-19 patients with moderate to severe symptoms, which are hospitalized and need urgent medical support. This was achieved by modifying a part of the antibody to avoid the activation of the immune system to prevent adverse reactions in the patients due to overshooting immune responses.

Prof. Dr. Michael Hust (TU Braunschweig), the lead senior author of this study and co-initiator of the CORAT initiative, comments: “The COR-101 antibody development project was only possible because of the close joint collaboration of our group with the YUMAB GmbH and the HZI. I’m optimistic, that this antibody will save many lives of COVID-19 patients.”

Dr. Maren Schubert (TU Braunschweig), co-senior author of this study, says: “We are proud to see the results of the research and development we started in February 2020 with the first production of SARS-CoV-2 proteins in insect cells.”

Prof. Dr. Stefan Dübel (TU Braunschweig), inventor of the antibody phage display technology, which was used to discover the antibody, and initiator of the CORAT initiative, emphasized: “We have demonstrated that we can develop effective therapeutic antibody drug candidates in a very short time. This knowledge will allow us to act faster and more specific in the next pandemic situation.”

Dr. Joop van den Heuvel, structure biologist at the HZI, adds: “We are fascinated about the mode of action of this unique antibody.”

Prof. Dr. Dr. Luka Čičin-Šain, head of the department „Viral Immunology“ at the HZI: “COR-101 shows the excellent capability of the Braunschweig region for translational infection research.”

Dr. André Frenzel, CSO of YUMAB and CORAT: “We are looking forward to see the clinical trial data of COR-101, an antibody which fills the current gap in the therapy of COVID-19 patients.”

About the study:

The study was conducted in the core research area “Infections and Therapeutics” at the TU Braunschweig. Mice and hamster were used for the studies. The animal experiments took place at the HZI and FU Berlin and were conducted under strict safety and animal protection regulations.

Original publication:

Bertoglio, F., Fühner. V., Ruschig, M., Abassi, L., Heine, P.A., Klünemann, T., Rand, U., Meier, D., Langreder, N., Steinke, S., Ballmann, R., Schneider, K.-T., Roth, K.D.R., Kuhn, P., Riese, P., Schäckermann, D., Korn, J., Koch, A., Chaudhry, M.Z., Eschke, K., Kim, Y., Zock-Emmenthal, S., Becker, M., Scholz, M., Moreira, G.M.S.G., Wenzel, E.V., Russo, G., Garritsen, H.S.P., Casu, S., Gerstner, A., Roth, G., Adler, J., Trimpert, J., Hermann, A., Schirrmann, T., Dübel, S., Frenzel, A., Van den Heuvel, J., Čičin-Šain, L., Schubert, M. & Hust, M. (2021). A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations. Cell Reports, Available online 7 July 2021, 109433, https://www.sciencedirect.com/science/article/pii/S2211124721008500

Wissenschaftliche Ansprechpartner:

Prof. Dr. Michael Hust
Technische Universität Braunschweig
Institute of Biochemistry, Biotechnology and Bioinformatics
Department of Biotechnology
Spielmannstraße 7
38106 Braunschweig
Germany
Phone: +49 531 391-5760
Mail: m.hust@tu-braunschweig.de
www.bbt.tu-bs.de/Biotech

Prof. Dr. Stefan Dübel
Technische Universität Braunschweig
Institute for Biochemistry, Biotechnology and Bioinformatics
Department of Biotechnology
Spielmannstraße 7
38106 Braunschweig
Germany
Phone: +49 531 391-5731
Mail: biotech@tu-braunschweig.de
www.bbt.tu-bs.de/Biotech

Originalpublikation:

https://www.sciencedirect.com/science/article/pii/S2211124721008500

Weitere Informationen:

https://magazin.tu-braunschweig.de/en/pi-post/cor-101-is-inhibiting-the-emerging…