Towards in silico design of targeted therapeutics
Grant ID: PT01224
Project leader: Adam Liwo
Implementers:
- Adam Liwo
- Nevena Ilieva
Uniwersytet Gdański
Wydział Chemii
Gdańsk
Start date: 2025-02-06
Planned end date: 2027-02-06
Project summary
This project aims to explore the potential of peptide aptamers grafted onto cyclotide scaffolds as antiviral agents targeting SARS-CoV-2 proteins. Peptide aptamers, combinatorial sequences of 5-20 amino acids, belong to the fastest-growing class of therapeutics – protein-based bioactive agents. They are gaining attention as alternatives to traditional drugs due to their small size, stability, and reduced immunogenicity. However, their experimental development is costly and complex. Integrating in silico approaches like molecular modelling and AI-based methods and techniques is a promising approach to address this challenge.
Cyclotides, highly stable cyclic peptides, provide an ideal framework for grafting aptamers, enhancing their stability, cellular uptake, and efficacy. This project focuses on designing aptamers against SARS-CoV-2 ORF6 and NSP13, proteins essential for viral replication and immune evasion. By inhibiting these targets, we aim to restore host immune responses, offering a novel antiviral strategy.
Both all-atom and coarse-grain approaches will be employed, particularly exploring new UNRES functionalities for modeling dynamic disulfide bridges, crucial in cyclotide design. Simulating systems of up to one million atoms demands substantial computational resources, highlighting the project's complexity and innovation in antiviral therapy development.
Cyclotides, highly stable cyclic peptides, provide an ideal framework for grafting aptamers, enhancing their stability, cellular uptake, and efficacy. This project focuses on designing aptamers against SARS-CoV-2 ORF6 and NSP13, proteins essential for viral replication and immune evasion. By inhibiting these targets, we aim to restore host immune responses, offering a novel antiviral strategy.
Both all-atom and coarse-grain approaches will be employed, particularly exploring new UNRES functionalities for modeling dynamic disulfide bridges, crucial in cyclotide design. Simulating systems of up to one million atoms demands substantial computational resources, highlighting the project's complexity and innovation in antiviral therapy development.
Publications
- D. Kaynarov, K. Marinova, R. Marinova, P. Petkov, L. Velkova, A. Dolashki, P. Petrov, L. Litov, E. Lilkova, P. Dolashka, N. Ilieva , In silico and physico-chemical characterization of cluster formation dynamics in peptide solutions, Biochemistry and Biophysics Reports 39, (2024) 101753
- Peicho Petkov, Nevena Ilieva, Elena Lilkova, Leandar Litov, Partitioning of Putative Antimicrobial Peptides into a Model Bacterial Membrane: a Metadynamics Approach, Advanced Computing in Industrial Mathematics: BGSIAM 2021, Studies in Computational Intelligence 522, (2025) 153-164
- N. Ilieva, P. Petkov, E. Lilkova, L. Velkova, P. Petrov, A. Dolashki, P. Dolashka, L. Litov, Toy Model of a Multi-Component Antimicrobial Substance with Novel Low-Molecular-Weight Snail-Mucus Peptides, Advanced Computing in Industrial Mathematics: BGSIAM 2023, Studies in Computational Intelligence 219, (2025) 1-13
- M. Rangelov, N. Todorova, P. Petkov, T. Nedeva, N. Ilieva, E. Lilkova, E. Krachmarova, L. Litov, In silico screening for potential inhibitors of the SARS-CoV-2 helicase Nsp13, Advanced Computing in Industrial Mathematics: BGSIAM 2023, Studies in Computational Intelligence 1219, (2025) 185-194
- Nevena Ilieva, Peicho Petkov, Elena Lilkova, and Leandar Litov, Metadynamics Study of Charged-Peptides Membrane-Destruction Potential, ) Large-Scale Scientific Computing. LSSC'23. Lecture Notes in Computer Science 00, (2025) 00
- Nevena Ilieva, Viruses and information flow: developing strategies for targeted antiviral therapies, Dynamics of Coding Matter and the Origin of Life (DYCOMAT) (March 14 & 15, 2024, Palma, Spain) 00, (2024) 00
- N. Ilieva, P. Petkov, E. Lilkova, and L. Litov, Disrupting Viral Sabotage: Computational Insights into SARS-CoV-2's Manipulation of Cellular Protein Synthesis and Strategies for Intervention, 14th National Congress on Theoretical and Applied Mechanics (Sofia, Bulgaria, 2-4th September 2024) 00, (2025) 00
- Nevena Ilieva, Bridging Biophysics and AI: Modeling Viral Proteins for Next-Generation Antivirals, 10th Conference of Vietnamese Researchers in Poland, CVRP2025 (15-16 November 2025, Warsaw, Poland) 00, (2025) 00
- Nevena Ilieva, From viral protein to antiviral lead, BGSIAM’2025 (10-12 December 2025, Sofia & online) 00, (2025) 00
- E. Lilkova, P. Petkov, N. Ilieva, L. Litov, Designing targeted therapeutics: computational insights and cyclotide engineering, BGSIAM’2025 (10-12 December 2025, Sofia & online) 00, (2025) 00
Contact
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tel.: + 48 58 347 24 11
email: office@task.gda.pl
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REGON: 000001620
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