Technology platform for new generations of drugs against diseases caused by coronaviruses, in particular SARS-CoV-2
Project title
Technology platform for new generations of drugs against diseases caused by coronaviruses, in particular SARS-CoV-2
Name of Beneficiary/Beneficiaries
Selvita S.A.
Name of programme
Operational Program “Smart Growth”
Competition
Fast Track – Coronaviruses
Project value
PLN 5,461,697.99
Funding value
PLN 2,893,334.72
Project delivery period
01.07.2021 – 31.10.2023
Our team
Selvita’s scientists involved in the project:
Dr. Georgiy Kachkovskyi: Project’s R&D Manager, leading a team of over 20 chemists on a daily basis. He has many years of experience in implementing integrated scientific projects in the field of organic and medicinal chemistry, also in the field of new drug discovery. Author and co-author of several publications and patents.
Chemist team:
Łukasz Indyk: Chemist associated with the project from the very beginning and employed in our company for over 7 years. Currently also a doctoral student at the Jagiellonian University. Responsible for verification and optimization of the synthetic methodology.
Dr. Viatcheslav Stepanenko: Senior scientist with extensive knowledge and experience in organic chemistry, which allowed him to look at chemical transformations from many different perspectives and propose countless alternative solutions.
Dr. Amanda Ferreira da Silva: Experienced chemist with specialization in NMR spectroscopy. Involved in the design and implementation of synthetic paths and in the analysis of spectroscopic data of compounds received by the entire team.
Mattia Piro: Young chemist who carries out even routine synthetic tasks with full commitment. His pharmaceutical background allowed him to actively participate in discussions on every topic related to the project.
Biologist team:
Olga Krzysztyńska-Kuleta: Head of the biology team. Responsible for planning, implementing and reporting results of biochemical experiments.
Dr. Patrycja Mrowiec-Kucharska: Biologist with an extensive experience in the area of high-throughput screening. She conducts biochemical tests of compounds in cooperation with Olga Krzysztyńska-Kuleta.
ADME Team:
Sylwia Wójtowicz: ADME specialist. Responsible for carrying out stability, solubility and lipophilicity tests of selected compounds.
Not shown in the photo:
Dr. Paulina Chęsy-Roman: ADME team leader with over 10 years of experience in chemical analytics.
Dr. Dorota Szczepaniak-Krupowska: Senior scientist – biologist. She works on a daily basis in the high-throughput screening team. Responsible for conducting biochemical experiments in the project.
Results of our work
The main result of our work are compounds with antiviral properties, which constitute the commercial library available in our company. Each compound we obtain is characterized and placed in a vial with a barcode enabling quick identification. As in the attached photo, the vials are arranged in boxes and stored in the compound repository.
The library includes over 1,000 different compounds – including fully characterized potential viral protease inhibitors and fragment compounds. An important structural element of many of our compounds is the difluoroketone moiety which is directly responsible for antiviral properties and translates into the uniqueness of the library. This type of moiety has not been used in the construction of the inhibitor molecules developed so far. The introduction of this structural element allows to block viral proteases – key enzymes in the virus development cycle. Enzymatic inhibition is achieved by creating a permanent bond between the reactive moiety and the catalytic cysteine residue located in the active center of most viral proteases, as shown in the diagram below. In this case, the enzymatic inhibition reaction leads to stopping the virus’s development cycle and neutralizing it.
When designing inhibitor structures, we aimed to achieve the greatest possible diversity within the library being created. In the construction of the final molecules, we used various reactive moieties containing a difluoroketone fragment. The mechanism of their action is in each case based on the formation of a permanent covalent bond with the catalytic amino acid in the active center, but the binding method depends on the initial structure. The illustration below schematically shows examples of some of the reactive moieties that we have successfully introduced into the compounds we have obtained, as well as methods of binding the structural fragments being created.
The obtained library of potential viral protease inhibitors has been included in a number of unique libraries available in our company. Based on them, Selvita offers screening services using automated cellular and biochemical tests. Experimental services are complemented by virtual screening options using molecular modeling methods and artificial intelligence (AI). More details about screening possibilities in our company and a description of commercial libraries can be found at the following links:
Issues addressed
Viral diseases constitute a serious health, social and economic problem worldwide. Current therapeutic strategies are often associated with many side effects or prove ineffective in the fight against viruses that mutate quickly. In this context, the development of new, effective antiviral therapies is particularly important.
The technological platform created as part of the project is based on a globally unique library of compounds with potential antiviral properties. The compounds included in the library were designed to be structurally similar to natural substances transformed by viral enzymes. The biological activity and associated therapeutic potential have been experimentally confirmed on a selected set of viral proteases from various virus species (including HIV and SARS-CoV-2). Additionally, the library has been partially characterized in terms of physicochemical properties, which will significantly speed up the process of developing drugs based on selected compounds.
The targeted compound library was created with the intention of conducting high-throughput screening studies using it. Selvita, as one of the largest biotechnology companies in Europe, providing services in the field of drug discovery and development, has adequate technological and human resources that enable efficient performance of this type of research, selection of candidates from the offered libraries and support of their further development.
Project beneficiaries
This technological platform, based on the targeted library of compounds, is part of a wide spectrum of screening services provided by Selvita. It is offered primarily to Polish and foreign pharmaceutical companies and scientific institutions interested in developing antiviral drugs and in research using compounds with antiviral properties. Thanks to the use of high-throughput screening tests using the described library of compounds, it is possible to develop innovative drugs for the treatment of viral infections, in particular those caused by coronaviruses. We hope that the project results will serve not only research purposes, but will ultimately enable the development of effective methods of treating viral diseases and, as a result, will benefit the entire society.
Major implementation challenges
By far the biggest challenge for us was the selection and optimization of a methodology suitable for the synthesis of the compounds we wanted. This was one of the key stages on the success of which the continuation of the entire project depended. The entire synthesis team’s hard work on several alternative methods ultimately resulted in a suitable method (and countless holes in our lab coats). To our relief, we avoided major problems in the later stages of the project.
Our advice to other applicants
We are fully satisfied with the results of our project. Our work shows how important innovative ideas and financial support are for achieving ambitious goals.
We encourage you to apply for support from EU funds. This is the first step to turning your ideas into reality, conducting important research and innovating. Thanks to support from the EU you can obtain not only funds for project implementation but also access to experts and a community of scientists who provide advice and support at every stage of the project.