12.06.2020 change 12.06.2020

Designing Anti-COVID-19 Drugs Easier Thanks to Polish Scientist

Credit: Adrian Wykrota Credit: Adrian Wykrota

A new online tool and database will help in the design of drugs too fight against COVID-19.

An international team of experts assembled by Professor Mariusz Jaskólski from the Adam Mickiewicz University in Poznań and the Institute of Bioorganic Chemistry PAS, verified coronavirus protein structures, fundamental for the development of anti-COVID-19 drugs.

As a result, they created the online tool capable of providing quality assessment of individual models, and in special cases also correcting detected shortcomings and errors.

Professor Jaskólski said: "We have thoroughly verified all models of SARS-CoV-2 coronavirus proteins and we present our results in a way that is understandable to recipients from broad biomedical circles. 

“Structural models, including those based on solid experimental data, always contain an element of original author's subjective interpretation and may sometimes be imperfect or even incorrect, especially if they were created in a hurry, which is understandable during the pandemic. 

“That is why it is so important that these models are verified and possibly corrected, and receive a quality mark from independent auditors.”

He added: “However, extensive remodelling was needed sometimes, especially in critical areas of protein-ligand interactions that directly affect drug design. The COVID-19 epidemiological crisis requires the highest accuracy of modelling of SARS-CoV-2 protein structures.”

Structure-assisted drug design experts working on COVID-19 have now received the new tool that to help them better understand the coronavirus and guarantee the correctness of the structural models, on which their work is based.

MODELS ARE KEY FOR DRUG DESIGN

Researchers use models at various stages of drug development. Models are used in structure-assisted design, to train computer algorithms that predict the best drugs, and to plan subsequent experiments. The accuracy of the start model plays a key role.

Due to the emergency situation caused by the pandemic, the majority of the SARS-CoV-2 coronavirus protein structure models are deposited at the Worlwide Protein Data Bank even before publication and before being thoroughly reviewed. 

Cooperating whenever possible with the authors of the original deposits, the 'auditors' are trying to replace the defective models in the Protein Data Bank with the correct ones.

Scientists working on Jaskólski's team include Dr. Alexander Wlodawer, National Cancer Institute (NCI), USA; Dr. Zbigniew Dauter, NCI & Argonne National Laboratory, USA; Dr. Ivan Shabalin, University of Virginia (UVA), USA; Professor Mirosław Gilski, Adam Mickiewicz University in Poznań and the Institute of Bioorganic Chemistry PAS; Dr. Dariusz Brzeziński, Poznan University of Technology, the Institute of Bioorganic Chemistry PAS and UVA; Dr. Marcin Kowiel, Institute of Bioorganic Chemistry PAS; Professor Wladek Minor, UVA; and Dr. Bernhard Rupp, k.k. Hofkristallamt, USA and the Medical University Innsbruck, Austria.

The team described their results and the publicly available online database of corrected structures in a Free Access article in the prestigious FEBS Journal: https://doi.org/10.1111/febs.15366.

Approx. 30 years ago, when the world feared an HIV pandemic, Professor Mariusz Jaskólski and Dr. Alexander Wlodawer determined the first protein structure of this retrovirus. Seven years later the first rationally designed anti-HIV drug was introduced. They later became the first winners of the Polish-American Scientific Award granted jointly by the Foundation for Polish Science and the American Association for the Advancement of Science (AAAS).

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