An international team of leading researchers from the Unites States Institutes of Health, the Argonne National Laboratory, the Polish Academy of Sciences and the University of Poznan, the University of Virginia, and the Division of Genetic Epidemiology of the Medical University Innsbruck provided the cover article for the FEBS Journal special issue on the Convid-19 pandemic (Figure 1).
The cover illustration by Marcin Minor summarizes the work of the team: the visualization of the key components of the SARS-CoV-2 coronavirus by X-ray crystallography and related methods provides valuable and indispensable information for the structure guided development of novel antiviral therapeutics.
Drug targets are proteins on the surface of the coronavirus, such as the spike protein that mediates the entry into the host cell by binding to the protease domain of the human angiotensin converting enzyme 2 (ACE2). Other important targets are viral proteases such as 3CLpro or PLpro whose inhibition by antiviral drugs blocks the assembly of new active viral particles.
The molecular structures of the viral drug targets are used in structure guided drug development to predict and optimize binding of inhibitors to the target proteins to either block viral entry or stop its replication. The success of this process critically depends on the quality of the molecular structures provided rapidly by many researchers world-wide. Only excellent structures can be used to precisely design and develop therapeutic drugs, and failure due to unsuitable structure models can be costly and delay the progress towards effective antivirals.
The SARS-CoV-2 Validation Team lead by Mariusz Jaskolski in Poznan validates the publicly deposited structures and team members correct and improve the structures, as necessary. The results are updated weekly and made available on a dedicated web site hosted at the University of Virginia, where scientists working on antiviral drug discovery can download improved structures models and retrieve validation results for newly deposited SARS-CoV-2 structures https://covid-19.bioreproducibility.org/.
The figure nearby summarizes the work of the SARS-CoV-2 Validation Team: carefully inspect the quality metrics and primary evidence, which for X-ray crystal structures is the electron density.
GENEPI research involved: Bernhard Rupp, an internationally recognized textbook author and expert in biomolecular crystallography and structure based drug lead discovery.
- Journal FEBS Volume 287, Issue 17, Focus Issue: COVID‐19
- Article: https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.15366
- Project site: https://covid-19.bioreproducibility.org/
- Bernhard Rupp: http://www.ruppweb.org/