The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread with devastating consequences. For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies. Here, we generated four neutralizing nanobodies that target the receptor-binding domain of the SARS-CoV-2 spike protein. We defined two distinct binding epitopes using x-ray crystallography and cryo-electron microscopy. Based on the structures, we engineered multivalent nanobodies with more than 100-fold improved neutralizing activity than monovalent nanobodies. Biparatopic nanobody fusions suppressed the emergence of escape mutants. Several nanobody constructs neutralized through receptor-binding competition, while other monovalent and biparatopic nanobodies triggered aberrant activation of the spike fusion machinery. These premature conformational changes in the spike protein forestalled productive fusion, and rendered the virions non-infectious.
New publication describes DiosCURE’s multivalent single-chain antibodies to inactivate SARS-CoV-2
DiosCURE SE announced a publication in
Science describing its core technology of multivalent single-chain antibodies with a unique molecular mode-of-action to inactivate SARS-CoV-2 virions. An international team led by scientists at the University of Bonn developed and characterized the lead candidates, which are exclusively licensed by DiosCURE.
This global pandemic requires an arsenal of therapeutic and preventative tools and our lead candidates will allow us to contribute to what will be an ongoing battle. DiosCURE was established with the goal of developing novel, best-in-class immunotherapies to protect a significant population which will remain at risk, including exposed healthcare workers, immunocompromised patients, non-responders to vaccines and patients experiencing post-acute COVID-19 syndrome. The data now published provides a solid foundation to continue our developm
E-Mail
(Philadelphia, PA) - Like a failing fuel pump that causes a loss of engine power in a car, a diseased heart can take a serious toll on the body s performance. For some patients, tasks like walking up a flight of stairs or walking across a room eventually turn into exhausting endeavors. This is because, over time, regardless of the underlying cause, heart damage typically progresses, owing to a constant barrage of oxidative stress and toxic lipids that alter heart cell energetics and, ultimately, the ability of the heart to function normally.
Oxidative stress occurs when harmful oxygen-containing molecules outnumber helpful antioxidants, leading to damaging reactions with proteins, DNA, and other cell components. Now, in two new studies, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) show that in the heart, one molecule in particular, Kruppel-like factor (KLF)-5, single-handedly fuels both the generation of oxidizing molecules and the accumul
Dr. Remi Martin-Fardon, Department of Molecular Medicine, The Scripps Research Institute
Associate Professor Tijana Jovanović-Talisman, Department of Molecular Medicine, Beckman Research Institute City of Hope,
The multidisciplinary team will study how ethanol, the cause of AUD, affects the opioid system function at the molecular, cellular and organism level, using a valid behavioral animal model of AUD, cells in culture, super-resolution fluorescence microscopy imaging and fluorescence correlation spectroscopy. Further Co-PIs of this project are Vladana Vukojevic and Björn Johansson from the Department of Clinical Neuroscience at Karolinska Institutet and Alessandra Matzeu from The Scripps Research Institute.
New medications are needed