Scientists of the solnatide network unravel the mechanism of action of Solnatide, a therapeutic candidate for ARDS treatment
APEPTICO Forschung und Entwicklung GmbH today announced that the mechanism of action of solnatide, a possible treatment for pulmonary oedema, has been disclosed by an international network of scientists from Austria, Spain and the United States.
Pulmonary permeability oedema is a life-threatening accumulation of fluid in the lungs, due to capillary leak either combined or not with impaired lung fluid clearance. It causes lack of oxygenation of the blood and can occur in patients with the Acute Respiratory Distress Syndrome (ARDS), which is the major complication in patients with severe COVID-19. The accumulation of liquid inside the lung’s airspace is linked to defects in the functioning of the epithelial sodium channel (ENaC), which can be induced by bacterial and viral toxins, including the spike protein of SARS-CoV-2. Pulmonary permeability oedema and lung tissue inflammation significantly contribute to the high mortality rate observed in patients with severe ARDS and severe COVID-19. Both of these medical conditions require invasive mechanical ventilation (IMV) and intensive care treatment.
The solnatide peptide (a.k.a. TIP peptide, AP301) was developed and characterized by Dr. Rudolf Lucas, Medical College of Georgia at Augusta University, USA. The Vienna company APEPTICO, the proprietary owner of solnatide, has been studying the biological function of this molecule for many years. Solnatide is currently being tested in clinical trials for the treatment of patients with moderate to severe ARDS as well with COVID-19.
The three-dimensional structural analysis of solnatide was led by Dr. Maria Macias, ICREA researcher and head of the Structural Characterization of Macromolecular Assemblies lab at IRB Barcelona, in collaboration with the APEPTICO scientific team and built upon earlier findings from Dr. Douglas Eaton’s (Emory) and Dr. Rudolf Lucas’ (Augusta University) research groups. Solnatide was manufactured by BCN Peptides in Barcelona.
Based on the conformational studies and in the analysis of charge distribution of the solnatide peptide surface, which has been published in the Computational and Structural Biotechnology Journal, the collaborators propose a model to describe how the solnatide peptide may interact with the cytoplasmic C-terminal domain of the ENaC-α subunit via electrostatic complementarity.
Commenting on the study, Dr. Bernhard Fischer, CEO of APEPTICO, stated: "In this regard, the work allowed the scientists to detail the mechanism of action of the solnatide peptide and its interaction with the sodium channel ENaC, which is responsible for the removal of pulmonary liquid in life-threatening conditions such as COVID-19-associated and non-COVID ARDS”.
Dr. Lucas commented “that the elegant analytical and molecular docking studies from Dr. Macias’ group not only confirmed earlier findings from his research, but actually further elucidated the mechanism of action of solnatide, which is a unique and direct activator of ENaC. In view of the importance of ENaC in both the alveolar and capillary endothelial compartments, this research will foster the development of novel peptide-based therapies for both non-COVID and COVID-ARDS, for which no proven pharmacological treatments exist to date”.
“Our work has focused on describing the structure of the peptide and proposing a mechanism of action to pave the way for possible improvements to its sequence, that is to say, small modifications that can make it more effective” added Dr. Macias.
This study received funding support from the European Commission (EC), Grant No. 101003595 and from the Austrian Research Promotion Agency (FFG), Grant No.880862.
Contact
Prof. Dr. Bernhard Fischer, CEO
APEPTICO Forschung und Entwicklung GmbH
Mariahilferstraße 136, Top 1.1.5
1150 Vienna, Austria
T: +43-664-1432919
F: +43-1-25330337795
E-mail: b.fischer@apeptico.com
URL: www.apeptico.com